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| ID | Type | Description | Link |
|---|---|---|---|
| 2022-502209-13-01 | Other Identifier | EU CT Number |
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| Name | Class |
|---|---|
| Hospital del Mar Research Institute (IMIM) | OTHER |
| Adknoma Health Research | INDUSTRY |
| Ministry of Science and Innovation, Spain | OTHER_GOV |
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The purpose of this First-in-Human Phase I study is to investigate the safety, tolerability and pharmacokinetics of CTH120 in adult healthy volunteers.
This trial is divided in three parts: FIH-CTH120-SAD (Single Ascending Doses), FIH-CTH120-MAD (Multiple Ascending Doses) and FIH-CTH120-FI (Food Interaction). FIH-CTH120-SAD will start first. The start of FIH-CTH120-MAD will await the results of at least three cohorts from the FIH-CTH120-SAD study before initiated. The starting dose of the FIH-CTH120-MAD will have been shown to be well tolerated in FIH-CTH120-SAD. FIH-CTH120-FI will be the last to start.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CTH120 | Experimental | Hard capsules of two strengths, 10 mg and 75 mg of CTH120 to be administered with 200 mL of water. CTH120 will be supplied by CONNECTA Therapeutics. Within each dose cohort group subjects (n=8) will be randomly assigned to the CTH120 dose or to the matching placebo in a 6 to 2 randomization ratio (placebo=2 and CTH120=6 per dose). |
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| Placebo | Placebo Comparator | Hard capsules of placebo to be administered with 200 mL of water. Placebo will be supplied by CONNECTA Therapeutics. Within each dose cohort group subjects (n=8) will be randomly assigned to the CTH120 dose or to the matching placebo in a 6 to 2 randomization ratio (placebo=2 and CTH120=6 per dose). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CTH120 | Drug | FIH-CTH120-SAD: Each independent cohort of 8 subjects (placebo=2 and CTH120=6 per dose) will receive a single administration of CTH120 or placebo. Four consecutive dose levels (20 mg/day, 40 mg/day, 85 mg/day and 160 mg/day) are planned. If no significant clinical adverse events are observed in the FIH-CTH120-SAD phase, an additional 5th cohort will be recruited to conduct the 5th dose level. FIH-CTH120-MAD: Each independent cohort of 8 subjects (placebo=2 and CTH120=6 per dose) will receive a daily administration of CTH120 or placebo for 7 days. Three consecutive dose levels are planned. The starting dose will be confirmed following the observed results of FIH-CTH120-SAD. FIH-CTH120-FI: One dosage of CTH120 will be assessed in 12 healthy male and female subjects in two conditions (Fed and Fasting). Subjects will be randomly assigned to 2 sequences: 6 subjects in a sequence "fed then fasting condition", 6 subjects in the reverse sequence ("fasting, then fed condition"). |
| Measure | Description | Time Frame |
|---|---|---|
| Treatment-emergent adverse events (TEAEs). | Primary Safety and Tolerability endpoint for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI). • AEs will be described in terms of result, frequency, intensity, medical decision, relation with study drug, as well as treatment received and subject retirement, duration, and time elapsed. AEs will also be listed and coded using the MedDRA Dictionary (version 26.0) for the term's codification. | From Day 1 to End-of-study: EOS will be on Day 8 (± 1 day) for FIH-CTH120-SAD and on Day 15 (+ 2 days) for FIH-CTH120-MAD |
| Treatment-emergent potentially clinically significant abnormalities (PSCAs) in blood pressure (mmHg) | Primary Safety and Tolerability endpoint for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI). • Blood pressure (mmHg) will be measured in the supine position following a 5 min rest. | From Day 1 to End-of-study (EOS): on Day 8 (± 1 day) for FIH-CTH120-SAD, and on Day 15 (+ 2 days) for FIH-CTH120-MAD |
| Treatment-emergent potentially clinically significant abnormalities (PSCAs) in pulse rate (bpm) | Primary Safety and Tolerability endpoint for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI). • Pulse rate (bpm) will be measured in the supine position following a 5 min rest. | From Day 1 to End-of-study (EOS): on Day 8 (± 1 day) for FIH-CTH120-SAD, and on Day 15 (+ 2 days) for FIH-CTH120-MAD |
| Treatment-emergent potentially clinically significant abnormalities (PSCAs) in oral body temperature (ºC) | Primary Safety and Tolerability endpoint for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI). • Oral body temperature (ºC) will be measured using an automated vital sign monitor device. | From Day 1 to End-of-study (EOS): on Day 8 (± 1 day) for FIH-CTH120-SAD, and on Day 15 (+ 2 days) for FIH-CTH120-MAD |
| Measure | Description | Time Frame |
|---|---|---|
| Observed maximum concentration (Cmax). | Secondary Pharmacokinetics endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI). • Plasma PK parameter calculated using a non-compartmental model: Cmax (ng/mL). | FIH-CTH120-SAD: On Day 1; FIH-CTH120-MAD: on Day 1, and Day 7 |
| Observed minimum concentration (Cmin). |
| Measure | Description | Time Frame |
|---|---|---|
| Area under the concentration-time curve (AUC0-24h, AUC0-t, AUC0-∞). | Exploratory objective (FIH-CTH120-FI). Plasma pharmacokinetics of the major metabolite of CTH120 after CTH120 single dose administration. • Plasma PK parameter calculated using a non-compartmental model: AUC0-24h (h * ng/mL), AUC0-t (h * ng/mL) AUC0-∞ (h * ng/mL). | FIH-CTH120-FI: AUC0-24h on Day 1; AUC0-t, AUC0-∞ where t is the last or the latest timepoint observed |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Rafael De la Torre, Pharm, PhD | Hospital del Mar Medical Research Institute (IMIM) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital del Mar Medical Research Institute (IMIM) | Barcelona | Barcelona | 08003 | Spain |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24448548 | Background | Myrick LK, Nakamoto-Kinoshita M, Lindor NM, Kirmani S, Cheng X, Warren ST. Fragile X syndrome due to a missense mutation. Eur J Hum Genet. 2014 Oct;22(10):1185-9. doi: 10.1038/ejhg.2013.311. Epub 2014 Jan 22. | |
| 28176767 | Background | Quartier A, Poquet H, Gilbert-Dussardier B, Rossi M, Casteleyn AS, Portes VD, Feger C, Nourisson E, Kuentz P, Redin C, Thevenon J, Mosca-Boidron AL, Callier P, Muller J, Lesca G, Huet F, Geoffroy V, El Chehadeh S, Jung M, Trojak B, Le Gras S, Lehalle D, Jost B, Maury S, Masurel A, Edery P, Thauvin-Robinet C, Gerard B, Mandel JL, Faivre L, Piton A. Intragenic FMR1 disease-causing variants: a significant mutational mechanism leading to Fragile-X syndrome. Eur J Hum Genet. 2017 Apr;25(4):423-431. doi: 10.1038/ejhg.2016.204. Epub 2017 Feb 8. |
| Label | URL |
|---|---|
| EMEA, "Committee for Medicinal Products for Human Use (CHMP) Guideline on strategies to identify and mitigate risks for first-in-human and early clinical trials with investigational medicinal products," EMEA/CHMP/SWP/28367/07, 2017 | View source |
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| ID | Term |
|---|---|
| D005600 | Fragile X Syndrome |
| D065886 | Neurodevelopmental Disorders |
| D002493 | Central Nervous System Diseases |
| D008607 | Intellectual Disability |
| D019954 | Neurobehavioral Manifestations |
| D040181 | Genetic Diseases, X-Linked |
| D000013 | Congenital Abnormalities |
| D035583 | Rare Diseases |
| ID | Term |
|---|---|
| D038901 | X-Linked Intellectual Disability |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D025064 | Sex Chromosome Disorders |
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FIH-CTH120-SAD: Prospective, monocentre, double-blind, randomized, placebo-controlled, subsequent-group, Phase I investigation to assess the safety, tolerability and pharmacokinetics of CTH120 administered orally in single ascending doses.
FIH-CTH120-MAD: Prospective, monocentre, double-blind, randomized, placebo-controlled, subsequent-groups, Phase I investigation to assess the safety, tolerability and pharmacokinetics of CTH120 administered orally in multiple ascending doses.
FIH-CTH120-FI: Prospective, open-label single dose, two-condition (fed versus fasting), two sequences, crossover Phase I investigation to assess the effects of food on the bioavailability of CTH120.
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FIH-CTH120-SAD and FIH-CTH120-MAD: double-blind, placebo-controlled trial preventing the knowledge of the study drug allocation. Thus, all trial stakeholders but the Pharmacy personnel will be blinded throughout the trial including the Sponsor personnel, the participating subjects, the study team at the investigational site, including the person administering the study drugs to the subject as well as the CRO personnel involved in the data management and statistical analysis.
FIH-CTH120-FI: open-label study.
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| Placebo | Other | FIH-CTH120-SAD: Each independent cohort of 8 subjects (placebo=2 and CTH120=6 per dose) will receive a single administration of CTH120 or placebo. Four consecutive dose levels (20 mg/day, 40 mg/day, 85 mg/day and 160 mg/day) are planned. If no significant clinical adverse events are observed in the FIH-CTH120-SAD phase, an additional 5th cohort will be recruited to conduct the 5th dose level. FIH-CTH120-MAD: Each independent cohort of 8 subjects (placebo=2 and CTH120=6 per dose) will receive a daily administration of CTH120 or placebo for 7 days. Three consecutive dose levels are planned. The starting dose will be confirmed following the observed results of FIH-CTH120-SAD. |
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| Treatment-emergent potentially clinically significant abnormalities (PSCAs) in electrocardiogram (ECG) values: normal sinus rhythm (NSR) |
Primary Safety and Tolerability endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI) • Computerized 12-lead electrocardiogram (ECG) recordings will be obtained. Each lead shall be recorded for at least 3 beats at a speed of 25 mm/s. Triplicate recordings will be made at the time points evaluated. The following parameter will be recorded: normal sinus rhythm (NSR). |
| From Day 1 to End-of-study (EOS): on Day 8 (± 1 day) for FIH-CTH120-SAD, and on Day 15 (+ 2 days) for FIH-CTH120-MAD |
| Treatment-emergent potentially clinically significant abnormalities (PSCAs) in electrocardiogram (ECG) values: heart rate (bpm) | Primary Safety and Tolerability endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI) • Computerized 12-lead electrocardiogram (ECG) recordings will be obtained. Each lead shall be recorded for at least 3 beats at a speed of 25 mm/s. Triplicate recordings will be made at the time points evaluated. The following parameter will be recorded: heart rate (bpm). | From Day 1 to End-of-study (EOS): on Day 8 (± 1 day) for FIH-CTH120-SAD, and on Day 15 (+ 2 days) for FIH-CTH120-MAD |
| Treatment-emergent potentially clinically significant abnormalities (PSCAs) in electrocardiogram (ECG) values: PR interval (ms) | Primary Safety and Tolerability endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI) • Computerized 12-lead electrocardiogram (ECG) recordings will be obtained. Each lead shall be recorded for at least 3 beats at a speed of 25 mm/s. Triplicate recordings will be made at the time points evaluated. The following parameter will be recorded: PR interval (ms). | From Day 1 to End-of-study (EOS): on Day 8 (± 1 day) for FIH-CTH120-SAD, and on Day 15 (+ 2 days) for FIH-CTH120-MAD |
| Treatment-emergent potentially clinically significant abnormalities (PSCAs) in electrocardiogram (ECG) values: QRS duration (ms) | Primary Safety and Tolerability endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI) • Computerized 12-lead electrocardiogram (ECG) recordings will be obtained. Each lead shall be recorded for at least 3 beats at a speed of 25 mm/s.Triplicate recordings will be made at the time points evaluated. The following parameter will be recorded: QRS duration (ms). | From Day 1 to End-of-study (EOS): on Day 8 (± 1 day) for FIH-CTH120-SAD, and on Day 15 (+ 2 days) for FIH-CTH120-MAD |
| Treatment-emergent potentially clinically significant abnormalities (PSCAs) in electrocardiogram (ECG) values: QT (ms) | Primary Safety and Tolerability endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI) • Computerized 12-lead electrocardiogram (ECG) recordings will be obtained. Each lead shall be recorded for at least 3 beats at a speed of 25 mm/s.Triplicate recordings will be made at the time points evaluated. The following parameter will be recorded: QT (ms). | From Day 1 to End-of-study (EOS): on Day 8 (± 1 day) for FIH-CTH120-SAD, and on Day 15 (+ 2 days) for FIH-CTH120-MAD |
| Treatment-emergent potentially clinically significant abnormalities (PSCAs) in electrocardiogram (ECG) values: QTcF (ms) | Primary Safety and Tolerability endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI) • Computerized 12-lead electrocardiogram (ECG) recordings will be obtained. Each lead shall be recorded for at least 3 beats at a speed of 25 mm/s.Triplicate recordings will be made at the time points evaluated. The following parameter will be recorded: QTcF (ms). | From Day 1 to End-of-study (EOS): on Day 8 (± 1 day) for FIH-CTH120-SAD, and on Day 15 (+ 2 days) for FIH-CTH120-MAD |
| Treatment-emergent potentially clinically significant abnormalities (PSCAs) in safety laboratory parameters: haematology | Primary Safety and Tolerability endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI). The following tests will be performed: • Haematology: complete blood count (complete blood count [CBC]; including haemoglobin, haematocrit, red blood cell [RBC], white blood cell (WBC), platelet count, and percent and absolute differential count (neutrophils, lymphocytes, eosinophils, monocytes, basophils, and other cells). | From Day 1 to End-of-study (EOS): on Day 8 (± 1 day) for FIH-CTH120-SAD, and on Day 15 (+ 2 days) for FIH-CTH120-MAD |
| Treatment-emergent potentially clinically significant abnormalities (PSCAs) in safety laboratory parameters: serum chemistry | Primary Safety and Tolerability endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI). The following tests will be performed: • Serum chemistry: sodium, potassium, chloride, non-fasting glucose, urea, creatinine, calcium, phosphate, magnesium, total and direct bilirubin, total protein, albumin, ALT, AST, ALP, lactate dehydrogenase. | From Day 1 to End-of-study (EOS): on Day 8 (± 1 day) for FIH-CTH120-SAD, and on Day 15 (+ 2 days) for FIH-CTH120-MAD |
| Treatment-emergent potentially clinically significant abnormalities (PSCAs) in safety laboratory parameters: coagulation | Primary Safety and Tolerability endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI). The following tests will be performed: • Coagulation parameters: activated partial thromboplastin time (aPTT), PT and INR. | From Day 1 to End-of-study (EOS): on Day 8 (± 1 day) for FIH-CTH120-SAD, and on Day 15 (+ 2 days) for FIH-CTH120-MAD |
| Treatment-emergent potentially clinically significant abnormalities (PSCAs) in safety laboratory parameters: urinalysis | Primary Safety and Tolerability endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI). The following tests will be performed: • Urinalysis parameters:
| From Day 1 to End-of-study (EOS): on Day 8 (± 1 day) for FIH-CTH120-SAD, and on Day 15 (+ 2 days) for FIH-CTH120-MAD |
| Psychometric tests: Hospital Anxiety/Depression rating Scale (HADS) | Primary Safety and Tolerability endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI). • HADS: Self-reported questionnaire used to detect depression and anxiety. It consists of 14 items (7 related to depression and 7 to anxiety) scored using a 4-point Likert scale (each item ranging from 0 to 3). Two scores are generated one for depression and one for anxiety each score ranging from 0 to 21. Higher scores indicate greater levels of anxiety or depression. Both scores can be categorized into: Normality (0-7); Probable case of anxiety or depression (8-10); Case of anxiety or depression (11-21). | FIH-CTH120-SAD: on Day -1 and Day 2; FIH-CTH120-MAD: on Day -1, Day 1, and Day 7 |
| Psychometric tests:Immediate Mood Scaler (IMS). | Primary Safety and Tolerability endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI). • IMS: The IMS is a tool to remotely and quickly track mood changes related to depression and anxiety in the moment. It consists of 22 items, scored between 1 and 7. The total score for this scale is the sum of the scores on all 22 items: ranging from 22 to 154. Lower scores reflect more negative mood states. | FIH-CTH120-SAD: on Day -1 and Day 2; FIH-CTH120-MAD: on Day -1, Day 1, and Day 7 |
| Area under the concentration-time curve (AUC0-24h, AUC0-t, AUC0-∞) after fed and fasting conditions. | Primary Pharmacokinetic endpoint for FIH-CTH120-FI (Not applicable for FIH-CTH120-SAD and FIH-CTH120-MAD). • Plasma PK parameter calculated using a non-compartmental model: AUC0-24h (h * ng/mL), AUC0-t (h * ng/mL) AUC0-∞ (h * ng/mL). | FIH-CTH120-FI: AUC0-24h on Day 1; AUC0-t, AUC0-∞ where t is the last or the latest timepoint observed |
| Observed maximum concentration (Cmax) after fed and fasting conditions. | Primary Pharmacokinetic endpoint for FIH-CTH120-FI (Not applicable for FIH-CTH120-SAD and FIH-CTH120-MAD) • Plasma PK parameter calculated using a non-compartmental model: Cmax (ng/mL). | FIH-CTH120-FI: On Day 1 of Period 1, and on Day 14/21/25 of Period 2 |
| Time to observed maximum concentration (tmax) after fed and fasting conditions. | Primary Pharmacokinetic endpoint for FIH-CTH120-FI (Not applicable for FIH-CTH120-SAD and FIH-CTH120-MAD) • Plasma PK parameter calculated using a non-compartmental model: tmax (h). | FIH-CTH120-FI: On Day 1 of Period 1, and on Day 14/21/25 of Period 2 |
Secondary Pharmacokinetics endpoints for FIH-CTH120-SAD, FIH-CTH120-MAD and FIH-CTH120-FI. • Plasma PK parameter calculated using a non-compartmental model: Cmin (ng/mL). |
| FIH-CTH120-SAD: On Day 2; FIH-CTH120-MAD: from Day 2 to Day 7 pre-dose and regularly after the last dose; FIH-CTH120-FI: on Day 2 of Period 1 and Day 15/22/29 of Period 2 |
| Time to observed maximum concentration (tmax). | Secondary Pharmacokinetics endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI). • Plasma PK parameter calculated using a non-compartmental model: tmax (h). | FIH-CTH120-SAD: On Day 1; FIH-CTH120-MAD: on Day 1, and Day 7 |
| Time to first measurable plasma concentration (tlag). | Secondary Pharmacokinetics endpoints for FIH-CTH120-SAD, FIH-CTH120-MAD and FIH-CTH120-FI. • Plasma PK parameter calculated using a non-compartmental model: tlag (h). | FIH-CTH120-SAD: On Day 1; FIH-CTH120-MAD: on Day 1, and Day 7; FIH-CTH120-FI: on Day 1 of Period 1 and on Day 14/21/25 of Period 2 |
| Time to last measurable plasma concentration (tlast). | Secondary Pharmacokinetics endpoints for FIH-CTH120-SAD, FIH-CTH120-MAD, and FIH-CTH120-FI. • Plasma PK parameter calculated using a non-compartmental model: tlast (h). | FIH-CTH120-SAD: On Day 2; FIH-CTH120-MAD: on Day 1, and Day 7; FIH-CTH120-FI: on Day 2 of Period 1 and Day 15/22/29 of Period 2 |
| Area under the concentration-time curve (AUC0-24h, AUC0-t, AUC0-∞). | Secondary Pharmacokinetics endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI). • Plasma PK parameter calculated using a non-compartmental model: AUC0-24h (h * ng/mL), AUC0-t (h * ng/mL) AUC0-∞ (h * ng/mL). | FIH-CTH120-SAD: AUC0-24h on Day 1; AUC0-t, AUC0-∞ where t is Day 8 (+/- 1 days) or the latest timepoint observed; FIH-CTH120-MAD: "AUC0-24h on Day 1 and Day 7; AUC0-t, AUC0-∞ after last dose, where t is Day 15 (+ 2 days) or the last timepoint observed |
| Terminal elimination half-life (t1/2). | Secondary Pharmacokinetics endpoints for FIH-CTH120-SAD, FIH-CTH120-MAD, and FIH-CTH120-FI. • Plasma PK parameter calculated using a non-compartmental model: t1/2 (h). | FIH-CTH120-SAD: from Day 1 to Day 8; FIH-CTH120-MAD: from Day 1 to Day 15; FIH-CTH120-FI: from Day 1 to Day28/35/42 |
| Apparent clearance (CL/F). | Secondary Pharmacokinetics endpoints for FIH-CTH120-SAD, FIH-CTH120-MAD, and FIH-CTH120-FI. • Plasma PK parameter calculated using a non-compartmental model: CL/F (mL/h * kg). | FIH-CTH120-SAD: from Day 1 to Day 8; FIH-CTH120-MAD: from Day 1 to Day 15; FIH-CTH120-FI: from Day 1 to Day28/35/42 |
| Apparent volume of distribution: Vd/F. | Secondary Pharmacokinetics endpoints for FIH-CTH120-SAD, FIH-CTH120-MAD, and FIH-CTH120-FI. • Plasma PK parameter calculated using a non-compartmental model: Vd/F (mL/kg). | FIH-CTH120-SAD: from Day 1 to Day 8; FIH-CTH120-MAD: from Day 1 to Day 15; FIH-CTH120-FI: from Day 1 to Day28/35/42 |
| Elimination rate constant (λz). | Secondary Pharmacokinetics endpoints for FIH-CTH120-SAD, FIH-CTH120-MAD, and FIH-CTH120-FI. • Plasma PK parameter calculated using a non-compartmental model: λz (1/h). | FIH-CTH120-SAD: from Day 1 to Day 8; FIH-CTH120-MAD: from Day 1 to Day 15; FIH-CTH120-FI: from Day 1 to Day28/35/42 |
| Serotonin (5-HT) metabolite profile. | Secondary Pharmacodynamic endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI). Concentrations of 5-Hydroxy indoleacetic acid (5-HIAA) (ng/mL). | FIH-CTH120-SAD: on Day 1 and Day 2; FIH-CTH120-MAD: on Day 1, Day 2, Day 7, and Day 8 |
| Noradrenaline (NA) metabolite profile. | Secondary Pharmacodynamic endpoints for FIH-CTH120-SAD and FIH-CTH120-MAD (Not applicable for FIH-CTH120-FI). Concentrations of 3-Methoxy-4-hydroxyphenylglycol (MHPG) (ng/mL). | FIH-CTH120-SAD: on Day 1 and Day 2; FIH-CTH120-MAD: on Day 1, Day 2, Day 7, and Day 8 |
| Treatment-emergent AEs (TAES). | Secondary Safety and tolerability endpoints (FIH-CTH120-FI). • AEs will be described in terms of result, frequency, intensity, medical decision, relation with study drug, as well as treatment received and subject retirement, duration, and time elapsed. AEs will also be listed and coded using the MedDRA Dictionary (version 26.0) for the term's codification. | FIH-CTH120-FI: from Day 1 to End-of-study. EOS will be on Day 28, or 35 or 42 (±1 day) depending on the length of the washout period determined |
| Treatment-emergent PSCAs in vital signs: blood pressure (mmHg) | Secondary Safety and tolerability endpoints (FIH-CTH120-FI). • Blood pressure (mmHg) will be measured in the supine position following a 5 min rest. | FIH-CTH120-FI: from Day 1 to End-of-study. EOS will be on Day 28, or 35 or 42 (±1 day) depending on the length of the washout period determined |
| Treatment-emergent PSCAs in vital signs: pulse rate (bpm) | Secondary Safety and tolerability endpoints (FIH-CTH120-FI). • Pulse rate (bpm) will be measured in the supine position following a 5 min rest. | FIH-CTH120-FI: from Day 1 to End-of-study. EOS will be on Day 28, or 35 or 42 (±1 day) depending on the length of the washout period determined |
| Treatment-emergent PSCAs in vital signs: Oral body temperature (ºC) | Secondary Safety and tolerability endpoints (FIH-CTH120-FI). • Oral body temperature (ºC) will be measured using an automated vital sign monitor device. | FIH-CTH120-FI: from Day 1 to End-of-study. EOS will be on Day 28, or 35 or 42 (±1 day) depending on the length of the washout period determined |
| Treatment-emergent PSCAs in ECG values: normal sinus rhythm (NSR) | Secondary Safety and tolerability endpoints (FIH-CTH120-FI). • Computerized 12-lead electrocardiogram (ECG) recordings will be obtained. Each lead shall be recorded for at least 3 beats at a speed of 25 mm/s. Triplicate recordings will be made at the time points evaluated. The following parameter will be recorded: normal sinus rhythm (NSR). | FIH-CTH120-FI: from Day 1 to End-of-study. EOS will be on Day 28, or 35 or 42 (±1 day) depending on the length of the washout period determined |
| Treatment-emergent PSCAs in ECG values: heart rate (bpm) | Secondary Safety and tolerability endpoints (FIH-CTH120-FI). • Computerized 12-lead electrocardiogram (ECG) recordings will be obtained. Each lead shall be recorded for at least 3 beats at a speed of 25 mm/s. Triplicate recordings will be made at the time points evaluated. The following parameters will be recorded: heart rate (bpm). | FIH-CTH120-FI: from Day 1 to End-of-study. EOS will be on Day 28, or 35 or 42 (±1 day) depending on the length of the washout period determined |
| Treatment-emergent PSCAs in ECG values: PR interval (ms) | Secondary Safety and tolerability endpoints (FIH-CTH120-FI). • Computerized 12-lead electrocardiogram (ECG) recordings will be obtained. Each lead shall be recorded for at least 3 beats at a speed of 25 mm/s. Triplicate recordings will be made at the time points evaluated. The following parameter will be recorded: PR interval (ms) | FIH-CTH120-FI: from Day 1 to End-of-study. EOS will be on Day 28, or 35 or 42 (±1 day) depending on the length of the washout period determined |
| Treatment-emergent PSCAs in ECG values: QRS duration (ms) | Secondary Safety and tolerability endpoints (FIH-CTH120-FI). • Computerized 12-lead electrocardiogram (ECG) recordings will be obtained. Each lead shall be recorded for at least 3 beats at a speed of 25 mm/s. Triplicate recordings will be made at the time points evaluated. The following parameter will be recorded: QRS duration (ms). | FIH-CTH120-FI: from Day 1 to End-of-study. EOS will be on Day 28, or 35 or 42 (±1 day) depending on the length of the washout period determined |
| Treatment-emergent PSCAs in ECG values: QT (ms) | Secondary Safety and tolerability endpoints (FIH-CTH120-FI). • Computerized 12-lead electrocardiogram (ECG) recordings will be obtained. Each lead shall be recorded for at least 3 beats at a speed of 25 mm/s. Triplicate recordings will be made at the time points evaluated. The following parameter will be recorded: QT (ms). | FIH-CTH120-FI: from Day 1 to End-of-study. EOS will be on Day 28, or 35 or 42 (±1 day) depending on the length of the washout period determined |
| Treatment-emergent PSCAs in ECG values: QTcF (ms) | Secondary Safety and tolerability endpoints (FIH-CTH120-FI). • Computerized 12-lead electrocardiogram (ECG) recordings will be obtained. Each lead shall be recorded for at least 3 beats at a speed of 25 mm/s. Triplicate recordings will be made at the time points evaluated. The following parameter will be recorded: QTcF (ms). | FIH-CTH120-FI: from Day 1 to End-of-study. EOS will be on Day 28, or 35 or 42 (±1 day) depending on the length of the washout period determined |
| Treatment-emergent PSCAs in safety laboratory parameters: haematology | Secondary Safety and tolerability endpoints (FIH-CTH120-FI). The following tests will be performed: • Haematology: complete blood count (complete blood count [CBC]; including haemoglobin, haematocrit, red blood cell [RBC], white blood cell (WBC), platelet count, and percent and absolute differential count (neutrophils, lymphocytes, eosinophils, monocytes, basophils, and other cells). | FIH-CTH120-FI: from Day 1 to End-of-study. EOS will be on Day 28, or 35 or 42 (±1 day) depending on the length of the washout period determined |
| Treatment-emergent PSCAs in safety laboratory parameters: serum chemistry | Secondary Safety and tolerability endpoints (FIH-CTH120-FI). The following tests will be performed: • Serum chemistry: sodium, potassium, chloride, non-fasting glucose, urea, creatinine, calcium, phosphate, magnesium, total and direct bilirubin, total protein, albumin, ALT, AST, ALP, lactate dehydrogenase. | FIH-CTH120-FI: from Day 1 to End-of-study. EOS will be on Day 28, or 35 or 42 (±1 day) depending on the length of the washout period determined |
| Treatment-emergent PSCAs in safety laboratory parameters: coagulation | Secondary Safety and tolerability endpoints (FIH-CTH120-FI). The following tests will be performed: • Coagulation parameters: activated partial thromboplastin time (aPTT), PT and INR. | FIH-CTH120-FI: from Day 1 to End-of-study. EOS will be on Day 28, or 35 or 42 (±1 day) depending on the length of the washout period determined |
| Treatment-emergent PSCAs in safety laboratory parameters: urinalysis | Secondary Safety and tolerability endpoints (FIH-CTH120-FI). The following tests will be performed: • Urinalysis parameters:
| FIH-CTH120-FI: from Day 1 to End-of-study. EOS will be on Day 28, or 35 or 42 (±1 day) depending on the length of the washout period determined |
| Psychometric tests: HADS | Secondary Safety and tolerability endpoints (FIH-CTH120-FI). • HADS: Self-reported questionnaire used to detect depression and anxiety. It consists of 14 items (7 related to depression and 7 to anxiety) scored using a 4-point Likert scale (each item ranging from 0 to 3). Two scores are generated one for depression and one for anxiety ranging each score ranging from 0 to 21. Higher scores indicate greater levels of anxiety or depression. Both scores can be categorized into: Normality (0-7); Probable case of anxiety or depression (8-10); Case of anxiety or depression (11-21). | FIH-CTH120-FI: On Day -1, Day 2, Day 13/20/27 and Day 15/22/29 |
| Psychometric tests: IMS | Secondary Safety and tolerability endpoints (FIH-CTH120-FI). • IMS: The IMS is a tool to remotely and quickly track mood changes related to depression and anxiety in the moment. It consists of 22 items, scored between 1 and 7. The total score for this scale is the sum of the scores on all 22 items: ranging from 22 to 154. Lower scores reflect more negative mood states. | FIH-CTH120-FI: On Day -1, Day 2, Day 13/20/27 and Day 15/22/29 |
| Observed maximum concentration (Cmax). | Exploratory objective (FIH-CTH120-FI). Plasma pharmacokinetics of the major metabolite of CTH120 after CTH120 single dose administration. • Plasma PK parameter calculated using a non-compartmental model: Cmax (ng/mL). | FIH-CTH120-FI: on Day 1 of Period 1 and on Day 14/21/25 of Period 2 |
| Time to observed maximum concentration (tmax). | Exploratory objective (FIH-CTH120-FI). Plasma pharmacokinetics of the major metabolite of CTH120 after CTH120 single dose administration. • Plasma PK parameter calculated using a non-compartmental model: tmax (h). | FIH-CTH120-FI: on Day 1 of Period 1 and on Day 14/21/25 of Period 2 |
| Observed minimum concentration (Cmin). | Exploratory objective (FIH-CTH120-FI). Plasma pharmacokinetics of the major metabolite of CTH120 after CTH120 single dose administration. • Plasma PK parameter calculated using a non-compartmental model: Cmin (ng/mL). | FIH-CTH120-FI: on Day 2 of Period 1 and Day 15/22/29 of Period 2 |
| Time to first measurable plasma concentration (tlag). | Exploratory objective (FIH-CTH120-FI). Plasma pharmacokinetics of the major metabolite of CTH120 after CTH120 single dose administration. • Plasma PK parameter calculated using a non-compartmental model: tlag (h). | FIH-CTH120-FI: on Day 1 of Period 1 and on Day 14/21/25 of Period 2 |
| Time to last measurable plasma concentration (tlast). | Exploratory objective (FIH-CTH120-FI). Plasma pharmacokinetics of the major metabolite of CTH120 after CTH120 single dose administration. • Plasma PK parameter calculated using a non-compartmental model: tlast (h). | FIH-CTH120-FI: on Day 2 of Period 1 and Day 15/22/29 of Period 2 |
| Terminal elimination half-life (t1/2). | Exploratory objective (FIH-CTH120-FI). • Plasma PK parameter calculated using a non-compartmental model: t1/2 (h). | FIH-CTH120-FI: from Day 1 to Day28/35/42 |
| Metabolic ratio Cmax (MR Cmax) | Exploratory objective (FIH-CTH120-FI). Plasma pharmacokinetics of the major metabolite of CTH120 after CTH120 single dose administration. • Plasma PK parameter calculated using a non-compartmental model: MR Cmax (n-fold). | FIH-CTH120-FI: from Day 1 to Day28/35/42 |
| Metabolic ratio AUC0-24 (MR AUC0-24) | Exploratory objective (FIH-CTH120-FI). Plasma pharmacokinetics of the major metabolite of CTH120 after CTH120 single dose administration. • Plasma PK parameter calculated using a non-compartmental model: MR AUC0-24 (n-fold) | FIH-CTH120-FI: from Day 1 to Day28/35/42 |
| Elimination rate constant (λz) | Exploratory objective (FIH-CTH120-FI). Plasma pharmacokinetics of the major metabolite of CTH120 after CTH120 single dose administration. • Plasma PK parameter calculated using a non-compartmental model: λz (1/h). | FIH-CTH120-FI: from Day 1 to Day28/35/42 |
| Renal clearance (CLr) | Exploratory objective (FIH-CTH120-FI). Urine pharmacokinetics of the major metabolite of CTH120 after CTH120 single dose administration. Renal clearance (L/h), as a Volume/time, calculated as CLr = Ae/PlasmaAUC0-∞, where Ae (µg) is the cumulative amount of unchanged drug excreted into the urine (0-48 h interval) and Plasma AUC0-∞ (ng.h/mL) is the area under the plasma concentration-time curve from time zero to infinity. | FIH-CTH120-FI: from Day 1 to Day28/35/42 |
| Amount excreted: absolute value as Ae | Exploratory objective (FIH-CTH120-FI). Urine pharmacokinetics of the major metabolite of CTH120 after CTH120 single dose administration. • The excreted amount will be calculated as absolute value as Ae: cumulative amount of unchanged drug excreted into the urine (interval) (µg). | FIH-CTH120-FI: from Day 1 to Day28/35/42 |
| Amount excreted: relative to dose as fe/F | Exploratory objective (FIH-CTH120-FI). Urine pharmacokinetics of the major metabolite of CTH120 after CTH120 single dose administration. • The excreted amount will be calculated as relative to dose as fe/F: fraction of the oral administered drug excreted into the urine (%). | FIH-CTH120-FI: from Day 1 to Day28/35/42 |
| Urinary excretion rate (UER) | Exploratory objective (FIH-CTH120-FI). Urine pharmacokinetics of the major metabolite of CTH120 after CTH120 single dose administration. The urinary excretion rate (μg/h) is the product of the urine flow rate (mL/h) and the urine analyte concentration (ng/mL), where:
| FIH-CTH120-FI: from Day 1 to Day28/35/42 |
| Urine elimination rate constant (h-1) | Exploratory objective (FIH-CTH120-FI). Urine pharmacokinetics of the major metabolite of CTH120 after CTH120 single dose administration. • Urine elimination rate constant (h-1): calculated as the slope (semilog plot) of the cumulative amount of drug excreted after each collection interval against the median of the collection interval. Nominal or actual times can be used as appropriate. | FIH-CTH120-FI: from Day 1 to Day28/35/42 |
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| D025063 | Chromosome Disorders |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D030342 | Genetic Diseases, Inborn |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D001523 | Mental Disorders |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |