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| Name | Class |
|---|---|
| University Ghent | OTHER |
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Mitochondrial Diseases are rare progressive, multi-system, often early fatal disorders affecting both children and adults. KH176 is a novel chemical entity currently under development for the treatment of inherited mitochondrial diseases, including MELAS (Mitochondrial Encephalomyopathy, Lactic acidosis, and Stroke-like episodes), Leigh's Disease and Leber's Hereditary Optic Neuropathy (LHON). KH176 is a potent intracellular redox modulating agent targeting the reactive oxygen species which are important in the pathogenesis of disorders of mitochondrial oxidative phosphorylation. After demonstrating a favourable safety profile in the pre-clinical testing, the safety, tolerability and pharmacokinetic and pharmacodynamic characteristics of the compound will now be evaluated in healthy male subjects in this trial
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Single Escalating | Experimental | 2 alternating groups receiving escalating single doses of active/placebo |
|
| Multiple Escalating | Experimental | 3 multiple escalating groups, receiving active/placebo |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| KH176 | Drug |
| ||
| placebo |
| Measure | Description | Time Frame |
|---|---|---|
| SAD: Change From Baseline in ECG Results by Timepoint: Corrected QT Interval According to Fridericia's Formula (QTcF) | The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation of the corrected QT intervals the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing. QTcF is calculated as the quotient between the QT interval in milliseconds and the cube root of the RR interval in seconds, according to Fridericia's formula. | Baseline, 1, 2, 4, 6, 8, 12, 24 hours, 7 day follow up |
| Pharmacodynamics of KH176 | Change from baseline in biochemistry related to Oxidative Phosphorylation (OXPHOS) (glutathione, lactate); MAD group | Day 1, day 7 |
| Relationship to Study Drug and Severity of Treatment-emergent Adverse Events | 4 months | |
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing) |
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Sedimentation Rate (SAD Group) | Baseline (pre-dose Day1), 24h post dose, FU (7 days after last dosing) | |
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Sedimentation Rate MAD Group |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Drug Research Unit Ghent | Ghent | Belgium |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29037240 | Derived | Koene S, Spaans E, Van Bortel L, Van Lancker G, Delafontaine B, Badilini F, Beyrath J, Smeitink J. KH176 under development for rare mitochondrial disease: a first in man randomized controlled clinical trial in healthy male volunteers. Orphanet J Rare Dis. 2017 Oct 16;12(1):163. doi: 10.1186/s13023-017-0715-0. |
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All studies were conducted at the Drug Research Unit Ghent. Participants agreed to stay in the Drug Research Unit during the first 24 h after dosing (SAD) and during Day 8 (MAD).
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| ID | Title | Description |
|---|---|---|
| FG000 | Single Ascending Group I | 2 alternating groups receiving escalating single doses of active/placebo KH176 placebo |
| FG001 | Single Ascending Group II | 2 alternating groups receiving escalating single doses of active/placebo KH176 placebo |
| FG002 | Multiple Ascending Group III | 3 multiple escalating groups, receiving active/placebo KH176 placebo |
| FG003 | Multiple Ascending Group IV | 3 multiple escalating groups, receiving active/placebo KH176 placebo |
| FG004 | Multiple Ascending Group V | 3 multiple escalating groups, receiving active/placebo KH176 placebo |
| FG005 | Placebo | Group receiving placebo |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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SAD:14 subjects divided in two groups of 7 subjects were included. Two subjects prematurely withdrew from the study after dosing period 2 for non-medical reasons. MAD part:18 subjects divided in 3 groups of 6 subjects were included. Two subjects prematurely withdrew from the study for non-medical reasons and were replaced.
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| ID | Title | Description |
|---|---|---|
| BG000 | SAD Group I | SAD group I: 10mg, 100mg, 800mg |
| BG001 | SAD Group II | SAD group II: 30mg, 300mg, 2000mg |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | SAD: Change From Baseline in ECG Results by Timepoint: Corrected QT Interval According to Fridericia's Formula (QTcF) | The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation of the corrected QT intervals the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing. QTcF is calculated as the quotient between the QT interval in milliseconds and the cube root of the RR interval in seconds, according to Fridericia's formula. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | msec | Baseline, 1, 2, 4, 6, 8, 12, 24 hours, 7 day follow up |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Group I Placebo | Placebo - single dose | 0 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA 18.1. | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Edwin Spaans, PharmD. | Khondrion B.V. | +31654997700 | spaans@khondrion.com |
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| ID | Term |
|---|---|
| D017241 | MELAS Syndrome |
| D007888 | Leigh Disease |
| D028361 | Mitochondrial Diseases |
| ID | Term |
|---|---|
| D017237 | Mitochondrial Encephalomyopathies |
| D017240 | Mitochondrial Myopathies |
| D009135 | Muscular Diseases |
| D009140 | Musculoskeletal Diseases |
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| ID | Term |
|---|---|
| C010643 | 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid |
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| Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days after last dosing) |
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit SAD Group | Hematocrit is a measure of the ratio of red blood cells (RBCs) in the blood by volume. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24 h postdose, FU (7 days after last dosing) |
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Haemoglobin. SAD | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24 h post dose, FU (7 days after last dosing) |
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Hemoglobin Concentration - SAD | Erythrocyte mean corpuscular hemoglobin concentration (MCHC) is a measure of the average concentration of hemoglobin per red blood cell. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24 h post dose, FU (7 days after last dosing) |
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Volume - SAD | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24 h post dose, FU (7 days after last dosing) |
| MAD: Change From Baseline in ECG Results by Time Point: QTcF | The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation of the corrected QT intervals the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple-dose part. QTcF is calculated as the quotient between the QT interval in milliseconds and the cube root of the RR interval in seconds, according to Fridericia's formula. | Baseline, Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7 |
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing) |
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Neutrophils. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing) |
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit MAD Group | Hematocrit is a measure of the ratio of red blood cells (RBCs) in the blood by volume. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) |
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing) |
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Thrombocytes. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h, FU (7 days post-dose) |
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value ateach timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post-dose) |
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post-dose) |
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Volume. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) |
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hemoglobin. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) |
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count. MAD | Blood samples were collected from participants at the indicated time points for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each time point are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) |
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Neutrophils. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) |
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Haemoglobin Concentration. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) |
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) |
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Hemoglobin. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) |
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) |
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) |
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) |
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Thrombocytes. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) |
| Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) |
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Aspartate Aminotransferase. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Total Protein. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Gamma-GT. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Alkaline Phosphatase. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Creatinine. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Chloride. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Total Bilirubin. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Alanine Aminotransferase. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Creatinine Kinase. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Urea. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Sodium. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Potassium. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Phosphate. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Calcium (Corrected for Albumin). SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Uric Acid. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Triiodothyronine (T3). SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Lipase. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: (Fasting) Glucose. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Human Serum Albumin. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Cholesterol. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: High Density Lipoproteins. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Triglycerides. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Low Density Lipoproteins. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Bicarbonate. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Thyroid-stimulating Hormone. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Thyroxine (T4). SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
| Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Lactate. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Total Protein. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline (pre-dose Day1), Day 3, Day 8, FU (one week after last dosing) |
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Alkaline Phosphatase. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline, Day 3, Day 8, FU (one week after last dosing) |
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Aspartate Aminotransferase. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline, Day 3, Day 8, FU (one week after last dosing) |
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Creatine Kinase. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline, Day 3, Day 8, FU (one week after last dosing) |
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Gamma GT. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline, Day 3, Day 8, FU (one week after last dosing) |
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Total Bilirubin. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline, Day 3, Day 8, FU (one week after last dosing) |
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Urea. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline, Day 3, Day 8, FU (one week after last dosing) |
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Creatinine. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline, Day 3, Day 8, FU (one week after last dosing) |
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Sodium. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline, Day 3, Day 8, FU (one week after last dosing) |
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Potassium. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline, Day 3, Day 8, FU (one week after last dosing) |
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Chloride. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline, Day 3, Day 8, FU (one week after last dosing) |
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Calcium (Corrected for Albumin). MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline, Day 3, Day 8, FU (one week after last dosing) |
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Uric Acid. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline, Day 3, Day 8, FU (one week after last dosing) |
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Lipase. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline, Day 3, Day 8, FU (one week after last dosing) |
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Alanine Aminotransferase. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline, Day 3, Day 8, FU (one week after last dosing) |
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Phosphate. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline, Day 3, Day 8, FU (one week after last dosing) |
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Human Serum Albumin. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline, Day 3, Day 8, FU (one week after last dosing) |
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Fasting Glucose. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline, Day 3, Day 8, FU (one week after last dosing) |
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Cholesterol. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline, Day 3, Day 8, FU (one week after last dosing) |
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Triglycerides. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline, Day 3, Day 8, FU (one week after last dosing) |
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Low Density Lipoproteins. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline, Day 3, Day 8, FU (one week after last dosing) |
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: High Density Lipoproteins. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline, Day 3, Day 8, FU (one week after last dosing) |
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Thyroid-stimulating Hormone. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline, Day 3, Day 8, FU (one week after last dosing) |
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Trilodothyronine (T3). MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline, Day 3, Day 8, FU (one week after last dosing) |
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Thyroxine (T4). MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline, Day 3, Day 8, FU (one week after last dosing) |
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Bicarbonate. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline, Day 3, Day 8, FU (one week after last dosing) |
| Change From Baseline in Chemistry Laboratory Test Results by Time Point: Lactate. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | Baseline, Day 3, Day 8, FU (one week after last dosing) |
| Phospholipidosis | Change from Day 1 to Day 7 in di-docosahexaenoyl (22:6)-bis(monoacylglycerol) phosphate (di-22:6-BMP) and normalized di-22:6-BMP (urine) - MAD | Day 1, Day 7 |
| MAD: Change From Baseline in ECG Results by Time Point: Corrected QT Interval According to Barret's Formaula (QTcB) | The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple- dose part. | Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up |
| MAD: Change From Baseline in ECG Results by Time Point: P Wave-Q Wave Interval (PQ Interval) | The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation of the PQ interval the average of the 3 recordings will be taken as baseline. | Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up |
| MAD: Change From Baseline in ECG Results by Time Point: the Interval That Denotes Depolarization of the Ventricles, Between the Beginning of the Q Wave and the End of the S Wave (QRS Interval) | The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple- dose part. | Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up |
| MAD: Change From Baseline in ECG Results by Time Point: QT Interval | The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple- dose part. | Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up |
| SAD: Change From Baseline in ECG Results by Time Point: PQ Interval | The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. | Pre-dose, Day 1, Day 7 |
| SAD: Change From Baseline in ECG Results by Time Point: QRS Interval | The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. | Pre-dose, Day 1, Day 7 |
| SAD: Change From Baseline in ECG Results by Time Point: QT Interval | The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. | Pre-dose, Day 1, Day 7 |
| SAD: Change From Baseline in ECG Results by Time Point: QTcB Interval | The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. | Pre-dose, Day1, Day 7 |
| Terminal Elimination Half-life (T1/2) of KH176 Over 24 Hours: SAD | Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d. | Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose |
| Terminal Elimination Half-life (T1/2) of KH183: SAD | Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d. | Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose |
| Maximum Concentration (Cmax) of KH176: SAD Group | Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d. | Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose |
| Maximum Concentration (Cmax) of KH183 Over 24 Hours: SAD | Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d. | Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose |
| Maximum Concentration (Cmax) of KH183 (Active Metabolite of KH176): MAD Group | Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.: Cmax was obtained directly from the concentration-time data. | Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours |
| Maximum Concentration (Cmax) of KH176: MAD | Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d. | pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours |
| Time to Maximum Concentration (Tmax) of KH176 Over 24 Hours: SAD | Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d. | Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose |
| Time to Reach Peak Plasma Concentration (Tmax) of KH183: SAD | Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d. | Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose |
| Time to Maximum Concentration (Tmax) of KH176 at Day 1, Day 7: MAD Group | Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d. | pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours |
| Time to Maximum Concentration (Tmax) of KH183 (Active Metabolite of KH176): MAD Group | Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.. tmax was obtained directly from the concentration-time data. | Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours |
| Accumulation Factor (Racc) of KH176 Over 7 Days: MAD Group | Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.. Racc was calculated as follows: AUCtau day 7/ AUCtau day 1. | Pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours |
| Accumulation Factor (Racc) of KH183 (Active Metabolite of KH176): MAD Group | Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.: Accumulation factor was calculated as follows: AUCtau day 7/ AUCtau day 1. | Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours |
| Area Under the Plasma Concentration Versus Time Curve (AUClast) of KH183: SAD Group | Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d. | Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose |
| Area Under the Plasma Concentration Versus Time Curve (AUClast) of KH176: SAD Group | Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d. | pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose |
| Area Under the Plasma Concentration-time Curve (AUCtau) of KH176: MAD Group: | Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d. | Pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours |
| Area Under the Plasma Concentration-time Curve During a Dose Interval (AUCtau) of KH183 (Active Metabolite of KH176): MAD Group | Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d. | Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours |
| Area Under the Plasma Concentration-time Curve From Time Zero Until Infinity (AUCl0-inf) of KH183: SAD | Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d. | Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose |
| Area Under the Plasma Concentration-time Curve From Time Zero Until Infinity (AUCl0-inf) of KH176: SAD | Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d. | Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose |
| KH176: Percentage of Administered Dose Excreted in Urine: SAD | Urine concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d. | 24 hours post-dose |
| KH183: Percentage of Administered Dose Excreted in Urine: SAD | Urine concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d. | 24 hours post-dose |
| KH176 + KH183: Percentage of Administered Dose Excreted in Urine: SAD | Urine concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d. | 24 hours post-dose |
| KH176: Percentage of Administered Dose Excreted in Urine: MAD | Urine concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d. | Day 7 post dose |
| KH183: Percentage of Administered Dose Excreted in Urine: MAD | Urine concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d. | Post dose Day 7 |
| KH173 + KH183: Percentage of Administered Dose Excreted in Urine: MAD | Urine concentrations of KH176 and KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d. | Day 7 Post dose |
| BG002 |
| MAD Group III |
MAD group III:100mg bis in die (BID) |
| BG003 | MAD Group IV | MAD group IV: 200mg BID |
| BG004 | MAD Group V | MAD group V: 400mg BID |
| BG005 | Placebo | Placebo group |
| BG006 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Height | Mean | Standard Deviation | cm |
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| Weight | Mean | Standard Deviation | kg |
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| BMI | Mean | Standard Deviation | kg/m^2 |
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Placebo - single dose
| OG001 | Group II Placebo | Placebo - single dose |
| OG002 | SAD Group I 10mg | 10mg KH176 - single dose |
| OG003 | SAD Group II 30mg | 30mg KH176 - single dose |
| OG004 | SAD Group I 100mg | 100mg KH176 - single dose |
| OG005 | SAD Group II 300mg | 300mg KH176 - single dose |
| OG006 | SAD Group I 800mg | 800mg KH176 - single dose |
| OG007 | SAD Group II 2000mg | 2000mg KH176 - single dose |
| OG008 | Group I Placebo + Food | Placebo + high calorie/high fat breakfast |
| OG009 | Group I 100mg + Food | 100mg KH176 + high calorie/high fat breakfast |
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| Primary | Pharmacodynamics of KH176 | Change from baseline in biochemistry related to Oxidative Phosphorylation (OXPHOS) (glutathione, lactate); MAD group | Per protocol set | Posted | Mean | Standard Deviation | ratio GSH/GSSG | Day 1, day 7 |
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| Primary | Relationship to Study Drug and Severity of Treatment-emergent Adverse Events | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Number | TEAE | 4 months |
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| Primary | Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | cells 10^6/µL | Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing) |
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| Primary | Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Sedimentation Rate (SAD Group) | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mm/hr | Baseline (pre-dose Day1), 24h post dose, FU (7 days after last dosing) |
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| Primary | Change From Baseline in Hematology Laboratory Test Results by Timepoint: Erythrocyte Sedimentation Rate MAD Group | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mm/hr | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days after last dosing) |
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| Primary | Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit SAD Group | Hematocrit is a measure of the ratio of red blood cells (RBCs) in the blood by volume. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | %red cells to the volume of whole blood. | Baseline (pre-dose Day 1), 24 h postdose, FU (7 days after last dosing) |
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| Primary | Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Haemoglobin. SAD | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | pg/cell | Baseline (pre-dose Day 1), 24 h post dose, FU (7 days after last dosing) |
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| Primary | Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Hemoglobin Concentration - SAD | Erythrocyte mean corpuscular hemoglobin concentration (MCHC) is a measure of the average concentration of hemoglobin per red blood cell. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | g/dL RBC | Baseline (pre-dose Day 1), 24 h post dose, FU (7 days after last dosing) |
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| Primary | Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Volume - SAD | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | fL | Baseline (pre-dose Day 1), 24 h post dose, FU (7 days after last dosing) |
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| Primary | MAD: Change From Baseline in ECG Results by Time Point: QTcF | The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation of the corrected QT intervals the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple-dose part. QTcF is calculated as the quotient between the QT interval in milliseconds and the cube root of the RR interval in seconds, according to Fridericia's formula. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | msec | Baseline, Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7 |
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| Primary | Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | cells 10^3/µL | Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing) |
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| Primary | Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | cells/µL | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
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| Primary | Change From Baseline in Hematology Laboratory Test Results by Timepoint: Neutrophils. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | cells/µL | Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing) |
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| Primary | Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hematocrit MAD Group | Hematocrit is a measure of the ratio of red blood cells (RBCs) in the blood by volume. Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | % of red cells to volume of whole blood. | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) |
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| Primary | Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | cells/µL | Baseline (pre-dose Day 1), 24h post dose, FU (7 days after last dosing) |
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| Primary | Change From Baseline in Hematology Laboratory Test Results by Timepoint: Thrombocytes. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | cells 10^3/µL | Baseline (pre-dose Day 1), 24h, FU (7 days post-dose) |
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| Primary | Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value ateach timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | cells/µL | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post-dose) |
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| Primary | Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | cells/µL | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post-dose) |
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| Primary | Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Volume. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | fL | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) |
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| Primary | Change From Baseline in Hematology Laboratory Test Results by Timepoint: Hemoglobin. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | g/dL | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) |
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| Primary | Change From Baseline in Hematology Laboratory Test Results by Timepoint: White Blood Cell Count. MAD | Blood samples were collected from participants at the indicated time points for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each time point are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | cells 10^3/µL | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) |
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| Primary | Change From Baseline in Hematology Laboratory Test Results by Timepoint: Neutrophils. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | cells/µL | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) |
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| Primary | Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Haemoglobin Concentration. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | g/dL RBC | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) |
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| Primary | Change From Baseline in Hematology Laboratory Test Results by Timepoint: Lymphocytes. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | cells/µL | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) |
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| Primary | Change From Baseline in Hematology Laboratory Test Results by Timepoint: Mean Corpuscular Hemoglobin. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | pg/cell | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) |
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| Primary | Change From Baseline in Hematology Laboratory Test Results by Timepoint: Red Blood Cell Count. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | cells 10^6/µL | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) |
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| Primary | Change From Baseline in Hematology Laboratory Test Results by Timepoint: Eosinophils. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | cells/µL | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) |
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| Primary | Change From Baseline in Hematology Laboratory Test Results by Timepoint: Monocytes. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | cells/µL | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) |
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| Primary | Change From Baseline in Hematology Laboratory Test Results by Timepoint: Thrombocytes. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | cells 10^3/µL | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) |
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| Primary | Change From Baseline in Hematology Laboratory Test Results by Timepoint: Basophils. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | cells/µL | Baseline (pre-dose Day 1), Day 3, Day 8, FU (7 days post dose) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Aspartate Aminotransferase. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | U/L | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Total Protein. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | g/L | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Gamma-GT. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | U/L | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Alkaline Phosphatase. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | U/L | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Creatinine. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mg/dL | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Chloride. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mmol/L | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Total Bilirubin. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mg/dL | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Alanine Aminotransferase. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | U/L | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Creatinine Kinase. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | U/L | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Urea. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mg/dL | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Sodium. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mmol/L | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Potassium. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mmol/L | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Phosphate. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mmol/L | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Calcium (Corrected for Albumin). SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mmol/L | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Uric Acid. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mg/dL | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Triiodothyronine (T3). SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | pg/mL | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Lipase. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | U/L | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Timepoint: (Fasting) Glucose. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mg/dL | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Human Serum Albumin. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | g/L | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Cholesterol. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mg/dL | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Timepoint: High Density Lipoproteins. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mg/dL | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Triglycerides. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mg/dL | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Low Density Lipoproteins. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mg/dL | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Bicarbonate. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mmol/L | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Thyroid-stimulating Hormone. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mU/L | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Thyroxine (T4). SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | ng/dL | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Timepoint: Lactate. SAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of clinical chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mg/dL | Baseline (pre-dose Day 1), 24h post dose, FU (7 days post dose) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Time Point: Total Protein. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of hematology parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | g/L | Baseline (pre-dose Day1), Day 3, Day 8, FU (one week after last dosing) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Time Point: Alkaline Phosphatase. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | U/L | Baseline, Day 3, Day 8, FU (one week after last dosing) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Time Point: Aspartate Aminotransferase. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | U/L | Baseline, Day 3, Day 8, FU (one week after last dosing) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Time Point: Creatine Kinase. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | U/L | Baseline, Day 3, Day 8, FU (one week after last dosing) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Time Point: Gamma GT. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | U/L | Baseline, Day 3, Day 8, FU (one week after last dosing) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Time Point: Total Bilirubin. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mg/dL | Baseline, Day 3, Day 8, FU (one week after last dosing) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Time Point: Urea. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mg/dL | Baseline, Day 3, Day 8, FU (one week after last dosing) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Time Point: Creatinine. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mg/dL | Baseline, Day 3, Day 8, FU (one week after last dosing) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Time Point: Sodium. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mmol/L | Baseline, Day 3, Day 8, FU (one week after last dosing) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Time Point: Potassium. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mmol/L | Baseline, Day 3, Day 8, FU (one week after last dosing) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Time Point: Chloride. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mmol/L | Baseline, Day 3, Day 8, FU (one week after last dosing) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Time Point: Calcium (Corrected for Albumin). MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mmol/L | Baseline, Day 3, Day 8, FU (one week after last dosing) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Time Point: Uric Acid. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mg/dL | Baseline, Day 3, Day 8, FU (one week after last dosing) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Time Point: Lipase. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | U/L | Baseline, Day 3, Day 8, FU (one week after last dosing) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Time Point: Alanine Aminotransferase. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | U/L | Baseline, Day 3, Day 8, FU (one week after last dosing) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Time Point: Phosphate. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mmol/L | Baseline, Day 3, Day 8, FU (one week after last dosing) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Time Point: Human Serum Albumin. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | g/L | Baseline, Day 3, Day 8, FU (one week after last dosing) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Time Point: Fasting Glucose. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mg/dL | Baseline, Day 3, Day 8, FU (one week after last dosing) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Time Point: Cholesterol. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mg/dL | Baseline, Day 3, Day 8, FU (one week after last dosing) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Time Point: Triglycerides. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mg/dL | Baseline, Day 3, Day 8, FU (one week after last dosing) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Time Point: Low Density Lipoproteins. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mg/dL | Baseline, Day 3, Day 8, FU (one week after last dosing) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Time Point: High Density Lipoproteins. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mg/dL | Baseline, Day 3, Day 8, FU (one week after last dosing) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Time Point: Thyroid-stimulating Hormone. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mU/L | Baseline, Day 3, Day 8, FU (one week after last dosing) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Time Point: Trilodothyronine (T3). MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | pg/mL | Baseline, Day 3, Day 8, FU (one week after last dosing) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Time Point: Thyroxine (T4). MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | ng/dL | Baseline, Day 3, Day 8, FU (one week after last dosing) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Time Point: Bicarbonate. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mmol/L | Baseline, Day 3, Day 8, FU (one week after last dosing) |
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| Primary | Change From Baseline in Chemistry Laboratory Test Results by Time Point: Lactate. MAD Group | Blood samples were collected from participants at the indicated timepoints for evaluation of chemistry parameters. The baseline value at visit and the change from baseline value at each timepoint are reported. The change from baseline value was calculated by subtracting the post-baseline value from the baseline value. | The safety analysis set included all subjects who have been assigned treatment and have been administered at least once with placebo or KH176. | Posted | Mean | Standard Deviation | mg/dL | Baseline, Day 3, Day 8, FU (one week after last dosing) |
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| Primary | Phospholipidosis | Change from Day 1 to Day 7 in di-docosahexaenoyl (22:6)-bis(monoacylglycerol) phosphate (di-22:6-BMP) and normalized di-22:6-BMP (urine) - MAD | Per protocol set | Posted | Mean | Standard Deviation | ng/mL | Day 1, Day 7 |
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| Primary | MAD: Change From Baseline in ECG Results by Time Point: Corrected QT Interval According to Barret's Formaula (QTcB) | The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple- dose part. | Safety Analysis Set | Posted | Mean | Standard Deviation | msec | Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up |
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| Primary | MAD: Change From Baseline in ECG Results by Time Point: P Wave-Q Wave Interval (PQ Interval) | The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation of the PQ interval the average of the 3 recordings will be taken as baseline. | Posted | Mean | Standard Deviation | msec | Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up |
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| Primary | MAD: Change From Baseline in ECG Results by Time Point: the Interval That Denotes Depolarization of the Ventricles, Between the Beginning of the Q Wave and the End of the S Wave (QRS Interval) | The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple- dose part. | Posted | Mean | Standard Deviation | msec | Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up |
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| Primary | MAD: Change From Baseline in ECG Results by Time Point: QT Interval | The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. Other ECG recordings will be singlet (one recording of at least 3 complexes) prior to dosing, or around the expected Cmax on Day 1 or 7 for the multiple- dose part. | Per protocol set | Posted | Mean | Standard Deviation | msec | Baseline (pre-dose Day 1), Day1, Day 2, Day 3, Day 4, Day 5, Day 6, Day 7, Follow-up |
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| Primary | SAD: Change From Baseline in ECG Results by Time Point: PQ Interval | The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. | Per protocol set | Posted | Mean | Standard Deviation | msec | Pre-dose, Day 1, Day 7 |
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| Primary | SAD: Change From Baseline in ECG Results by Time Point: QRS Interval | The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. | Per protocol set | Posted | Mean | Standard Deviation | msec | Pre-dose, Day 1, Day 7 |
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| Primary | SAD: Change From Baseline in ECG Results by Time Point: QT Interval | The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. | Per protocol set | Posted | Mean | Standard Deviation | msec | Pre-dose, Day 1, Day 7 |
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| Primary | SAD: Change From Baseline in ECG Results by Time Point: QTcB Interval | The baseline ECG recording consists of a triplicate recording (3 recordings of a least 3 complexes within a 5 minute window) prior to dosing on Day 1. For the evaluation the average of the 3 recordings will be taken as baseline. | Per protocol set | Posted | Mean | Standard Deviation | msec | Pre-dose, Day1, Day 7 |
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| Primary | Terminal Elimination Half-life (T1/2) of KH176 Over 24 Hours: SAD | Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d. | Per protocol set | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose |
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| Primary | Terminal Elimination Half-life (T1/2) of KH183: SAD | Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d. | Per protocol set | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose |
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| Primary | Maximum Concentration (Cmax) of KH176: SAD Group | Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d. | Per protocol set | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose |
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| Primary | Maximum Concentration (Cmax) of KH183 Over 24 Hours: SAD | Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d. | Per protocol set | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose |
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| Primary | Maximum Concentration (Cmax) of KH183 (Active Metabolite of KH176): MAD Group | Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.: Cmax was obtained directly from the concentration-time data. | Per protocol set | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours |
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| Primary | Maximum Concentration (Cmax) of KH176: MAD | Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d. | Per protocol set | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours |
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| Primary | Time to Maximum Concentration (Tmax) of KH176 Over 24 Hours: SAD | Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d. | Per protocol set | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose |
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| Primary | Time to Reach Peak Plasma Concentration (Tmax) of KH183: SAD | Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d. | Per protocol set | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose |
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| Primary | Time to Maximum Concentration (Tmax) of KH176 at Day 1, Day 7: MAD Group | Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d. | Per protocol set | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours |
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| Primary | Time to Maximum Concentration (Tmax) of KH183 (Active Metabolite of KH176): MAD Group | Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.. tmax was obtained directly from the concentration-time data. | Per protocol set | Posted | Geometric Mean | Geometric Coefficient of Variation | hours | Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours |
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| Primary | Accumulation Factor (Racc) of KH176 Over 7 Days: MAD Group | Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.. Racc was calculated as follows: AUCtau day 7/ AUCtau day 1. | Per protocol set | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours |
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| Primary | Accumulation Factor (Racc) of KH183 (Active Metabolite of KH176): MAD Group | Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d.: Accumulation factor was calculated as follows: AUCtau day 7/ AUCtau day 1. | Per protocol set. The placebo subjects were excluded from the PK analysis per-protocol set. | Posted | Geometric Mean | Geometric Coefficient of Variation | ratio | Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours |
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| Primary | Area Under the Plasma Concentration Versus Time Curve (AUClast) of KH183: SAD Group | Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d. | Per protocol set | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose |
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| Primary | Area Under the Plasma Concentration Versus Time Curve (AUClast) of KH176: SAD Group | Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d. | Per protocol set | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose |
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| Primary | Area Under the Plasma Concentration-time Curve (AUCtau) of KH176: MAD Group: | Plasma concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d. | Per protocol set | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Pre-dose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours |
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| Primary | Area Under the Plasma Concentration-time Curve During a Dose Interval (AUCtau) of KH183 (Active Metabolite of KH176): MAD Group | Plasma concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d. | Per protocol set. The placebo subjects were excluded from the PharmaocoKinetics (PK) analysis per-protocol set. | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Predose at Day 1, 2, 4, 7, and post-dose at Day 1 and Day 7 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 hours |
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| Primary | Area Under the Plasma Concentration-time Curve From Time Zero Until Infinity (AUCl0-inf) of KH183: SAD | Plasma concentrations of KH183 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d. | Per protocol set | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose |
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| Primary | Area Under the Plasma Concentration-time Curve From Time Zero Until Infinity (AUCl0-inf) of KH176: SAD | Plasma concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food) , 300mg, 800mg, 2000mg b.i.d. | Per protocol set | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Pre-dose (5 min before dosing) and 0.5, 1, 1.5, 2, 3, 6, 8, 12, and 24 hours post-dose |
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| Primary | KH176: Percentage of Administered Dose Excreted in Urine: SAD | Urine concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d. | Per protocol set | Posted | Geometric Mean | Geometric Coefficient of Variation | percentage of dose excreted | 24 hours post-dose |
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| Primary | KH183: Percentage of Administered Dose Excreted in Urine: SAD | Urine concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d. | Per protocol set | Posted | Geometric Mean | Geometric Coefficient of Variation | percentage of dose excreted | 24 hours post-dose |
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| Primary | KH176 + KH183: Percentage of Administered Dose Excreted in Urine: SAD | Urine concentrations of KH176 were analysed after single dose administration of doses 10mg, 30mg, 100mg (with and without food), 300mg, 800mg, 2000mg b.i.d. | Per protocol set | Posted | Geometric Mean | Geometric Coefficient of Variation | percentage of dose excreted | 24 hours post-dose |
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| Primary | KH176: Percentage of Administered Dose Excreted in Urine: MAD | Urine concentrations of KH176 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d. | Per protocol set. The placebo subjects were excluded from the Pharmacokinetics (PK) analysis per-protocol set. | Posted | Geometric Mean | Geometric Coefficient of Variation | percentage of dose excreted | Day 7 post dose |
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| Primary | KH183: Percentage of Administered Dose Excreted in Urine: MAD | Urine concentrations of KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d. | Per protocol set. The placebo subjects were excluded from the Pharmacokinetics (PK) analysis per-protocol set. | Posted | Geometric Mean | Geometric Coefficient of Variation | percentage of dose excreted | Post dose Day 7 |
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| Primary | KH173 + KH183: Percentage of Administered Dose Excreted in Urine: MAD | Urine concentrations of KH176 and KH183 were analysed after multiple-dose administration of doses of 100, 200 and 400 mg b.i.d. | Per protocol set. The placebo subjects were excluded from the Pharmacokinetics (PK) analysis per-protocol set. | Posted | Geometric Mean | Geometric Coefficient of Variation | percentage of dose excreted | Day 7 Post dose |
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| 6 |
| 0 |
| 6 |
| 2 |
| 6 |
| EG001 | Group II Placebo | Placebo - single dose | 0 | 6 | 0 | 6 | 1 | 6 |
| EG002 | SAD Group I 10mg | 10mg KH176 - single dose | 0 | 4 | 0 | 4 | 2 | 4 |
| EG003 | SAD Group II 30mg | 30mg KH176 - single dose | 0 | 4 | 0 | 4 | 3 | 4 |
| EG004 | SAD Group I 100mg | 100mg KH176 - single dose | 0 | 4 | 0 | 4 | 4 | 4 |
| EG005 | SAD Group II 300mg | 300mg KH176 - single dose | 0 | 4 | 0 | 4 | 1 | 4 |
| EG006 | SAD Group I 800mg | 800mg KH176 - single dose | 0 | 4 | 0 | 4 | 0 | 4 |
| EG007 | SAD Group II 2000mg | 2000mg KH176 - single dose | 0 | 4 | 0 | 4 | 4 | 4 |
| EG008 | Group I Placebo + Food | Placebo + high calorie/high fat breakfast | 0 | 2 | 0 | 2 | 1 | 2 |
| EG009 | Group I 100mg + Food | 100mg KH176 + high calorie/high fat breakfast | 0 | 4 | 0 | 4 | 1 | 4 |
| EG010 | MAD Group III 200mg | 100mg BID/Day (over 7 days) | 0 | 4 | 0 | 4 | 3 | 4 |
| EG011 | MAD Group IV 400mg | 200mg BID/Day (over 7 days) | 0 | 4 | 0 | 4 | 3 | 4 |
| EG012 | MAD Group V 800mg | 400mg BID/Day (over 7 days) | 0 | 4 | 0 | 4 | 4 | 4 |
| EG013 | Placebo | Placebo | 0 | 6 | 0 | 6 | 5 | 6 |
| Bradyphrenia | Psychiatric disorders | MedDRA 18.1. | Non-systematic Assessment |
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| Depersonalisation | Psychiatric disorders | MedDRA 18.1. | Non-systematic Assessment |
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| Hallucination, visual | Psychiatric disorders | MedDRA 18.1. | Non-systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 18.1. | Non-systematic Assessment |
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| Dysgeusia | Psychiatric disorders | MedDRA 18.1. | Non-systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 18.1. | Non-systematic Assessment |
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| Presyncope | Nervous system disorders | MedDRA 18.1. | Non-systematic Assessment |
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| Brundle branch block right | Cardiac disorders | MedDRA 18.1. | Non-systematic Assessment |
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| Oropharyngeal discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1. | Non-systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 18.1. | Non-systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 18.1. | Non-systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 18.1. | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 18.1. | Non-systematic Assessment |
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| Odynophagia | Gastrointestinal disorders | MedDRA 18.1. | Non-systematic Assessment |
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| Paraesthesia oral | Gastrointestinal disorders | MedDRA 18.1. | Non-systematic Assessment |
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| Retching | Gastrointestinal disorders | MedDRA 18.1. | Non-systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 18.1. | Non-systematic Assessment |
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| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 18.1. | Non-systematic Assessment |
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| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA 18.1. | Non-systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 18.1. | Non-systematic Assessment |
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| Catheter site pain | General disorders | MedDRA 18.1. | Non-systematic Assessment |
|
| Chills | General disorders | MedDRA 18.1. | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA 18.1. | Non-systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA 18.1. | Non-systematic Assessment |
|
| Malaise | General disorders | MedDRA 18.1. | Non-systematic Assessment |
|
| Blood pressure diastolic increased | Investigations | MedDRA 18.1. | Non-systematic Assessment |
|
| Blood pressure systolic increased | Investigations | MedDRA 18.1. | Non-systematic Assessment |
|
| Electrocardiogram QT prolonged | Investigations | MedDRA 18.1. | Non-systematic Assessment |
|
| Eosinophil count increased | Investigations | MedDRA 18.1. | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 18.1. | Non-systematic Assessment |
|
| Nightmare | Psychiatric disorders | MedDRA 18.1. | Non-systematic Assessment |
|
| Head discomfort | Nervous system disorders | MedDRA 18.1. | Non-systematic Assessment |
|
| Conjunctival haemorrhage | Eye disorders | MedDRA 18.1. | Non-systematic Assessment |
|
| Eye irritation | Eye disorders | MedDRA 18.1. | Non-systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA 18.1. | Non-systematic Assessment |
|
| Rash macular | Skin and subcutaneous tissue disorders | MedDRA 18.1. | Non-systematic Assessment |
|
| Skin irritation | Skin and subcutaneous tissue disorders | MedDRA 18.1. | Non-systematic Assessment |
|
| Polyuria | Renal and urinary disorders | MedDRA 18.1. | Non-systematic Assessment |
|
| Feeling cold | General disorders | MedDRA 18.1. | Non-systematic Assessment |
|
| Feeling hot | General disorders | MedDRA 18.1. | Non-systematic Assessment |
|
| Blood creatinine phosphokinase increased | Investigations | MedDRA 18.1. | Non-systematic Assessment |
|
| Lipase increased | Investigations | MedDRA 18.1. | Non-systematic Assessment |
|
| Wound | Injury, poisoning and procedural complications | MedDRA 18.1. | Non-systematic Assessment |
|
Not provided
Not provided
| D020739 | Brain Diseases, Metabolic, Inborn |
| D001928 | Brain Diseases, Metabolic |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D059345 | Cerebral Small Vessel Diseases |
| D002561 | Cerebrovascular Disorders |
| D009468 | Neuromuscular Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D008661 | Metabolism, Inborn Errors |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D015323 | Pyruvate Metabolism, Inborn Errors |
| D002239 | Carbohydrate Metabolism, Inborn Errors |
| GSH/GSSG Day 7-0h |
|
| GSH/GSSG Day 7-3h |
|
| GSH/GSSG Day 7-6h |
|
| GSH/GSSG Day 7-12h |
|
| Serious TEAE |
|
| Not related TEAE |
|
| Unlikely related |
|
| Possibly related |
|
| Related |
|
| Change from BL at 24h |
|
| Change from BL at FU |
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| Change from BL at 24h |
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| Change from BL at FU |
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| Change from BL at Day 3 |
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| Change from BL at Day 8 |
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| Change from BL at FU |
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| Change from BL at 24h |
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| Change from BL at FU |
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| Change from BL at 24h - Day 1 |
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| Change from BL at FU |
|
| Change from BL at 24h - Day 1 |
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| Change from BL at FU |
|
| Change from BL at 24h |
|
| Change from BL at FU |
|
| Change from BL at 2h - Day 1 |
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| Change from BL at 24h - Day 1 |
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| Change from BL Day 7 at 1h - Day 7 |
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| Change from BL Day 7 at 2h - Day 7 |
|
| Change from BL Day 7 at 4h |
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| Change from BL Day 7 BL at 6h - Day 7 |
|
| Change from BL Day 7 at 8h - Day 7 |
|
| Change from BL Day 7 at 12h - Day 7 |
|
| Change from BL at pre-dose Day 2 |
|
| Change from BL at pre-dose Day 3 |
|
| Change from BL at pre-dose Day 4 |
|
| Change from BL at pre-dose Day 5 |
|
| Change from BL at pre-dose Day 6 |
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| Change from BL at pre-dose Day 7 |
|
| Change from BL at FU |
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| Change from BL at 24h |
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| Change from BL at FU |
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| Change from BL at 24h |
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| Change from BL at FU |
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| Change from BL at 24h |
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| Change from BL at FU |
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| Change from BL at Day 3 |
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| Change from BL at Day 8 |
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| Change from BL at FU |
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| Change from BL at 24h |
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| Change from BL at FU |
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| Change from BL at 24h |
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| Change from BL at FU |
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| Change from BL at 24h |
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| Change from BL at FU |
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| Change from BL at 24h |
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| Change from BL at FU |
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| Change from BL at Day 3 |
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| Change from BL at Day 8 |
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| Change from BL at FU |
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| Change from BL at Day 3 |
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| Change from BL at Day 8 |
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| Change from BL at FU |
|
| Change from BL at Day 3 |
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| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at 24h |
|
| Change from BL at FU |
|
| Change from BL at 24h |
|
| Change from BL at FU |
|
| Change from BL at 24h |
|
| Change from BL at FU |
|
| Change from BL at 24h |
|
| Change from BL at FU |
|
| Change from BL at 24h |
|
| Change from BL at FU |
|
| Change from BL at 24h |
|
| Change from BL at FU |
|
| Change from BL at 24h |
|
| Change from BL at FU |
|
| Change from BL at 24h |
|
| Change from BL at FU |
|
| Change from BL at 24h |
|
| Change from BL at FU |
|
| Change from BL at 24h |
|
| Change from BL at FU |
|
| Change from BL at 24h |
|
| Change from BL at FU |
|
| Change from BL at 24h |
|
| Change from BL at FU |
|
| Change from BL at 24h |
|
| Change from BL at FU |
|
| Change from BL at 24h |
|
| Change from BL at FU |
|
| Change from BL at 24h |
|
| Change from BL at FU |
|
| Change from BL at 24h |
|
| Change from BL at FU |
|
| Change from BL at 24h |
|
| Change from BL at FU |
|
| Change from BL at 24h |
|
| Change from BL at FU |
|
| Change from BL at 24h |
|
| Change from BL at FU |
|
| Change from BL at 24h |
|
| Change from BL at FU |
|
| Change from BL at 24h |
|
| Change from BL at FU |
|
| Change from BL at 24h |
|
| Change from BL at FU |
|
| Change from BL at 24h |
|
| Change from BL at FU |
|
| Change from BL at 24h |
|
| Change from BL at FU |
|
| Change from BL at 24h |
|
| Change from BL at FU |
|
| Change from BL at 24h |
|
| Change from BL at FU |
|
| Change from BL at 24h |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Change from BL at Day 3 |
|
| Change from BL at Day 8 |
|
| Change from BL at FU |
|
| Normalized di-22:6-BMP: Change from Day 1 to Day 7 |
|
| Change from baseline at 2h - Day 1 |
|
| Change from BL at 24h - Day 1 |
|
| Baseline (pre-dose Day 7) |
|
| Change from pre-dose Day 7 at 1h - Day 7 |
|
| Change from pre-dose Day 7 at 2h - Day 7 |
|
| Change from pre-dose Day 7 at 4h |
|
| Change from pre-dose Day 7 BL at 6h - Day 7 |
|
| Change from pre-dose Day 7 at 8h - Day 7 |
|
| Change from pre-dose Day 7 at 12h - Day 7 |
|
| Change from BL at pre-dose Day 2 |
|
| Change from BL at pre-dose Day 3 |
|
| Change from BL at pre-dose Day 4 |
|
| Change from BL at pre-dose Day 5 |
|
| Change from BL at pre-dose Day 6 |
|
| Change from BL at pre-dose Day 7 |
|
| Change from BL at FU |
|
| Change from baseline at 2h - Day 1 |
|
| Change from BL at 24h - Day 1 |
|
| Baseline (pre-dose Day 7) |
|
| Change from pre-dose Day 7 at 1h - Day 7 |
|
| Change from pre-dose Day 7 at 2h - Day 7 |
|
| Change from pre-dose Day 7 at 4h |
|
| Change from pre-dose Day 7 BL at 6h - Day 7 |
|
| Change from pre-dose Day 7 at 8h - Day 7 |
|
| Change from pre-dose Day 7 at 12h - Day 7 |
|
| Change from BL at pre-dose Day 2 |
|
| Change from BL at pre-dose Day 3 |
|
| Change from BL at pre-dose Day 4 |
|
| Change from BL at pre-dose Day 5 |
|
| Change from BL at pre-dose Day 6 |
|
| Change from BL at pre-dose Day 7 |
|
| Change from BL at FU |
|
| Change from BL at 2h - Day 1 |
|
| Change from BL at 24h - Day 1 |
|
| Baseline (pre-dose Day 7) |
|
| Change from BL Day 7 at 1h - Day 7 |
|
| Change from BL Day 7 at 2h - Day 7 |
|
| Change from BL Day 7 at 4h |
|
| Change from BL Day 7 BL at 6h - Day 7 |
|
| Change from BL Day 7 at 8h - Day 7 |
|
| Change from BL Day 7 at 12h - Day 7 |
|
| Change from BL at pre-dose Day 2 |
|
| Change from BL at pre-dose Day 3 |
|
| Change from BL at pre-dose Day 4 |
|
| Change from BL at pre-dose Day 5 |
|
| Change from BL at pre-dose Day 6 |
|
| Change from BL at pre-dose Day 7 |
|
| Change from BL at FU |
|
| Change from BL at 2h - Day 1 |
|
| Change from BL at 24h - Day 1 |
|
| Baseline (pre-dose Day 7) |
|
| Change from pre-dose Day 7 at 1h - Day 7 |
|
| Change from pre-dose Day 7 at 2h - Day 7 |
|
| Change from pre-dose Day 7 at 4h |
|
| Change from pre-dose Day 7 BL at 6h - Day 7 |
|
| Change from pre-dose Day 7 at 8h - Day 7 |
|
| Change from pre-dose Day 7 at 12h - Day 7 |
|
| Change from BL at pre-dose Day 2 |
|
| Change from BL at pre-dose Day 3 |
|
| Change from BL at pre-dose Day 4 |
|
| Change from BL at pre-dose Day 5 |
|
| Change from BL at pre-dose Day 6 |
|
| Change from BL at pre-dose Day 7 |
|
| Change from BL at FU |
|
| Change from baseline at 1h |
|
| Change from BL at 2h post dose |
|
| Change from BL at 4h post dose |
|
| Change from BL at 6h post dose |
|
| Change from BL at 8h post dose |
|
| Change from BLat 12h post dose |
|
| Change from BL at 24h post dose |
|
| Change from BL at FU |
|
| Change from baseline at 1h |
|
| Change from BL at 2h post dose |
|
| Change from BL at 4h post dose |
|
| Change from BL at 6h post dose |
|
| Change from BL at 8h post dose |
|
| Change from BL at 12h post dose |
|
| Change from BL at 24h post dose |
|
| Change from BL at FU |
|
| Change from baseline at 1h |
|
| Change from BL at 2h post dose |
|
| Change from BL at 4h post dose |
|
| Change from BL at 6h post dose |
|
| Change from BL at 8h post dose |
|
| Change from BL at 12h post dose |
|
| Change from BL at 24h post dose |
|
| Change from BL at FU |
|
| Change from BL at 1h |
|
| Change from BL at 2h post dose |
|
| Change from BL at 4h post dose |
|
| Change from BL at 6h post dose |
|
| Change from BL at 8h post dose |
|
| Change from BL at 12h post dose |
|
| Change from BL at 24h post dose |
|
| Change from BL at FU |
|
|
|
|
|
|
|