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The purpose of this study is to evaluate the safety, tolerability and pharmacokinetics of RT001 in patients with Friedreich's ataxia.
Study RT001-002 is a randomized, double-blind, controlled, ascending dose study to evaluate the safety, tolerability, pharmacokinetic, disease state, and exploratory endpoints in patients with Friedreich's ataxia after oral administration. The study includes 2 dose levels of RT001.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| RT001, oral, 1.8 g/day | Experimental | RT001, oral, 1.8 g QD for 28 days or matching comparator |
|
| RT001, oral, 9 g/day | Experimental | RT001, oral, 4.5 g BID for 28 days or matching comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Low dose cohort | Drug | RT001 is encapsulated di-deutero synthetic homologue of linoleic acid ethyl ester. Each capsule contains 900 mg of RT001. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With Adverse Events | 28 days |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetics - Area Under the Concentration-time Curve After a Single Dose | AUC 0-24 hours post-dose (Hours -1.0 to -0.5 (pre-breakfast, pre-dose), 0.5 (± 5 min), 1 (± 5 min), 1.5 (± 5 min), 2 (± 10 min), 4 (± 10 min) (pre-lunch), 6 (± 10 min), 8 (± 10 min), 12 (± 10 min), and 16 (± 30 min) Day 2: 24 hours following dosing on Day 1 (± 30 min; pre-breakfast, pre-dose) was measured for the low and high dose cohorts after a single dose of RT001 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Curtis Scribner, MD | Biojiva LLC | Study Director |
| Theresa Zesiewicz, MD | USF Ataxia Research Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Collaborative Neuroscience Network, LLC | Long Beach | California | 90806 | United States | ||
| University of South Florida |
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 - RT001 (1.8 g/Day) | RT001, oral, 2 capsules/day RT001: RT001 is encapsulated di-deutero synthetic homologue of linoleic acid ethyl ester. Each capsule contains 900 mg of RT001. |
| FG001 | Cohort 1 - Comparator | RT001 comparator, oral, 2 capsules/day RT001 comparator: RT001 comparator is encapsulated non-deuterated linoleic acid ethyl ester. |
| FG002 | Cohort 2 - RT001 (9 g/Day) | RT001, oral, 10 capsules/day RT001: RT001 is encapsulated di-deutero synthetic homologue of linoleic acid ethyl ester. Each capsule contains 900 mg of RT001. |
| FG003 | Cohort 2 - Comparator | RT001 comparator, oral, 10 capsules/day RT001 comparator: RT001 comparator is encapsulated non-deuterated linoleic acid ethyl ester. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 - RT001 | RT001 - 2 capsules/day (1.8 g/day) |
| BG001 | Cohort 1 - Comparator | RT001 comparator - 2 capsules/day |
| Units | Counts |
|---|---|
| Participants |
|
| 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 | Number of Patients With Adverse Events | Posted | Number | participants | 28 days |
|
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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 | Cohort 1 - RT001 (1.8 g/Day) | RT001, oral, 2 capsules/day RT001: RT001 is encapsulated di-deutero synthetic homologue of linoleic acid ethyl ester. Each capsule contains 900 mg of RT001. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Steatorrhea requiring overnight hospitalization | Gastrointestinal disorders | Systematic Assessment | The subject developed severe steatorrhea after a single dose of RT001. This required overnight hospitalization. The condition resolved after within 24 hours after drug discontinuation. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal discomfort | Gastrointestinal disorders | Systematic Assessment | Most of the TEAEs were mild gastrointestinal distress due to the fat content of the study drug (both active and the comparator.) They were self-limited. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Frederic Heerinckx/VP Clinical Operations | Retrotope, Inc | 650-437-0700 | 109 | frederic@retrotope.com |
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| ID | Term |
|---|---|
| D005621 | Friedreich Ataxia |
| ID | Term |
|---|---|
| D013132 | Spinocerebellar Degenerations |
| D002526 | Cerebellar Diseases |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| D015331 | Cohort Studies |
| C000634027 | RT001 |
| ID | Term |
|---|---|
| D016021 | Epidemiologic Studies |
| D016020 | Epidemiologic Study Characteristics |
| D004812 | Epidemiologic Methods |
| D008919 | Investigative Techniques |
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|
| High dose cohort | Drug | RT001 comparator is encapsulated non-deuterated linoleic acid ethyl ester. |
|
|
| 24 hours |
| Pharmacokinetics - Maximum Observed Plasma Concentration After a Single Dose | Plasma levels were measured for the following time points: Day 1: Hours -1.0 to -0.5 (pre-breakfast, pre-dose), 0.5 (± 5 min), 1 (± 5 min), 1.5 (± 5 min), 2 (± 10 min), 4 (± 10 min) (pre-lunch), 6 (± 10 min), 8 (± 10 min), 12 (± 10 min), and 16 (± 30 min) Day 2: 24 hours following dosing on Day 1 (± 30 min; pre-breakfast, pre-dose) PK curves were constructed from these data and CMax measured on the curves for the low and high dose cohorts | 24 hours |
| Pharmacokinetics - Time to Reach Maximum Plasma Concentration After a Single Dose | TMax measured for the low and high dose cohorts | 24 hours |
| Pharmacokinetics - Maximum Observed Plasma Concentration After Final Dose on Day 28 | After 28 days of dosing, the final dose of RT001 was administered, and PK samples were obtained at the following timepoints (all timepoints refer to final dose on Day 28): Day 28: Hours -1.0 to -0.5 (pre-breakfast, pre-dose on Day 28), 0.5 (± 5 min), 1 (± 5 min), 1.5 (± 5 min), 2 (± 10 min), 4 (± 10 min) (pre-lunch), 6 (± 10 min), 8 (± 10 min), 12 (± 10 min), and 16 (± 30 min) Day 29: Hours 24 (± 30 min; pre-breakfast) and 32 (± 30 min) hours following final dose on Day 28 Day 30: 48 hours following final dose on Day 28 (± 30 min; pre-breakfast) Day 31: 72 hours following final dose on Day 28 (± 30 min; pre-breakfast) PK curves were constructed, and CMax at 28 days was determined from these curves | Day 28-Day 31 (3 days) |
| Pharmacokinetics - Terminal Half-life Estimation After Final Dose on Day 28 | After 28 days of dosing, the final dose of RT001 was administered, and PK samples were obtained at the following timepoints (all timepoints refer to final dose on Day 28): Day 28: Hours -1.0 to -0.5 (pre-breakfast, pre-dose on Day 28), 0.5 (± 5 min), 1 (± 5 min), 1.5 (± 5 min), 2 (± 10 min), 4 (± 10 min) (pre-lunch), 6 (± 10 min), 8 (± 10 min), 12 (± 10 min), and 16 (± 30 min) Day 29: Hours 24 (± 30 min; pre-breakfast) and 32 (± 30 min) hours following final dose on Day 28 Day 30: 48 hours following final dose on Day 28 (± 30 min; pre-breakfast) Day 31: 72 hours following final dose on Day 28 (± 30 min; pre-breakfast) PK curves were constructed, and T1/2 at 28 days was determined from these curves | Day 28-Day 31 (3 days) |
| Change From Baseline at 28 Days in the Timed 25 Foot Walk (T25FW) | The T25FW is a quantitative mobility and leg function performance test based on a timed 25-foot walk. T25FW was measured at baseline and at 28 days. These data were compared. | 28 days |
| Change From Baseline at 28 Days in the Friedreich Ataxia Rating Scale (FARS) - Neurological Score (Minimum Score 0, Maximum Score 125, Lower is Better) | The FARS-neurological rating scale specifically developed and validated for Friedreich's Ataxia. The FARS-Neurological included evaluations of the neurological signs that specifically reflect neural substrates affected in patients with FA. Based on a neurological examination bulbar (11 points), upper limb coordination (36 points), lower limb coordination (16 points), peripheral nervous system (26 points), and upright stability (36 points) functions were assessed for individual sub-scores (11, 36, 16, 26, and 36) with a maximum score of 125 (Friedreich's Ataxia Study Group, Subramony et al., 2005, Lynch et al., 2006). FARS-Neurologic examinations were conducted by a qualified physician or health professional trained in the use of the FARS format. A lower score is better. The minimum score is 0, the maximum score is 125. | 28 days |
| Change From Baseline at 28 Days in Peak Workload for the Treated Population vs. the Comparator Population | Peak workload was measured using cardiopulmonary exercise testing at baseline and after 28 days of treatment. The results of treatment were compared to baseline examination. | 28 days |
| Tampa |
| Florida |
| 33612 |
| United States |
| BG002 | Cohort 2 - RT001 | RT001 - 10 capsules/day (9 g/day) |
| BG003 | Cohort 2 - Comparator | RT001 comparator - 10 capsules/day |
| BG004 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Race/Ethnicity, Customized | Number | participants |
|
| Body Mass Index (BMI) | Mean | Standard Deviation | kg/m^2 |
|
| OG003 | Cohort 2 - Comparator | RT001 comparator, oral, 10 capsules/day RT001 comparator: RT001 comparator is encapsulated non-deuterated linoleic acid ethyl ester. |
|
|
| Secondary | Pharmacokinetics - Area Under the Concentration-time Curve After a Single Dose | AUC 0-24 hours post-dose (Hours -1.0 to -0.5 (pre-breakfast, pre-dose), 0.5 (± 5 min), 1 (± 5 min), 1.5 (± 5 min), 2 (± 10 min), 4 (± 10 min) (pre-lunch), 6 (± 10 min), 8 (± 10 min), 12 (± 10 min), and 16 (± 30 min) Day 2: 24 hours following dosing on Day 1 (± 30 min; pre-breakfast, pre-dose) was measured for the low and high dose cohorts after a single dose of RT001 | Posted | Mean | Standard Deviation | ug*h/mL | 24 hours |
|
|
|
| Secondary | Pharmacokinetics - Maximum Observed Plasma Concentration After a Single Dose | Plasma levels were measured for the following time points: Day 1: Hours -1.0 to -0.5 (pre-breakfast, pre-dose), 0.5 (± 5 min), 1 (± 5 min), 1.5 (± 5 min), 2 (± 10 min), 4 (± 10 min) (pre-lunch), 6 (± 10 min), 8 (± 10 min), 12 (± 10 min), and 16 (± 30 min) Day 2: 24 hours following dosing on Day 1 (± 30 min; pre-breakfast, pre-dose) PK curves were constructed from these data and CMax measured on the curves for the low and high dose cohorts | Posted | Mean | Standard Deviation | ug/mL | 24 hours |
|
|
|
| Secondary | Pharmacokinetics - Time to Reach Maximum Plasma Concentration After a Single Dose | TMax measured for the low and high dose cohorts | Posted | Mean | Standard Deviation | h | 24 hours |
|
|
|
| Secondary | Pharmacokinetics - Maximum Observed Plasma Concentration After Final Dose on Day 28 | After 28 days of dosing, the final dose of RT001 was administered, and PK samples were obtained at the following timepoints (all timepoints refer to final dose on Day 28): Day 28: Hours -1.0 to -0.5 (pre-breakfast, pre-dose on Day 28), 0.5 (± 5 min), 1 (± 5 min), 1.5 (± 5 min), 2 (± 10 min), 4 (± 10 min) (pre-lunch), 6 (± 10 min), 8 (± 10 min), 12 (± 10 min), and 16 (± 30 min) Day 29: Hours 24 (± 30 min; pre-breakfast) and 32 (± 30 min) hours following final dose on Day 28 Day 30: 48 hours following final dose on Day 28 (± 30 min; pre-breakfast) Day 31: 72 hours following final dose on Day 28 (± 30 min; pre-breakfast) PK curves were constructed, and CMax at 28 days was determined from these curves | Posted | Mean | Standard Deviation | ug/mL | Day 28-Day 31 (3 days) |
|
|
|
| Secondary | Pharmacokinetics - Terminal Half-life Estimation After Final Dose on Day 28 | After 28 days of dosing, the final dose of RT001 was administered, and PK samples were obtained at the following timepoints (all timepoints refer to final dose on Day 28): Day 28: Hours -1.0 to -0.5 (pre-breakfast, pre-dose on Day 28), 0.5 (± 5 min), 1 (± 5 min), 1.5 (± 5 min), 2 (± 10 min), 4 (± 10 min) (pre-lunch), 6 (± 10 min), 8 (± 10 min), 12 (± 10 min), and 16 (± 30 min) Day 29: Hours 24 (± 30 min; pre-breakfast) and 32 (± 30 min) hours following final dose on Day 28 Day 30: 48 hours following final dose on Day 28 (± 30 min; pre-breakfast) Day 31: 72 hours following final dose on Day 28 (± 30 min; pre-breakfast) PK curves were constructed, and T1/2 at 28 days was determined from these curves | Posted | Mean | Standard Deviation | h | Day 28-Day 31 (3 days) |
|
|
|
| Secondary | Change From Baseline at 28 Days in the Timed 25 Foot Walk (T25FW) | The T25FW is a quantitative mobility and leg function performance test based on a timed 25-foot walk. T25FW was measured at baseline and at 28 days. These data were compared. | Posted | Mean | Standard Deviation | sec | 28 days |
|
|
|
| Secondary | Change From Baseline at 28 Days in the Friedreich Ataxia Rating Scale (FARS) - Neurological Score (Minimum Score 0, Maximum Score 125, Lower is Better) | The FARS-neurological rating scale specifically developed and validated for Friedreich's Ataxia. The FARS-Neurological included evaluations of the neurological signs that specifically reflect neural substrates affected in patients with FA. Based on a neurological examination bulbar (11 points), upper limb coordination (36 points), lower limb coordination (16 points), peripheral nervous system (26 points), and upright stability (36 points) functions were assessed for individual sub-scores (11, 36, 16, 26, and 36) with a maximum score of 125 (Friedreich's Ataxia Study Group, Subramony et al., 2005, Lynch et al., 2006). FARS-Neurologic examinations were conducted by a qualified physician or health professional trained in the use of the FARS format. A lower score is better. The minimum score is 0, the maximum score is 125. | Posted | Mean | Standard Deviation | units on a scale maximum 125 | 28 days |
|
|
|
| Secondary | Change From Baseline at 28 Days in Peak Workload for the Treated Population vs. the Comparator Population | Peak workload was measured using cardiopulmonary exercise testing at baseline and after 28 days of treatment. The results of treatment were compared to baseline examination. | Subjects unable to start or complete the test were excluded from analysis. Treatment and comparator cohorts were pooled to allow for statistical analysis. | Posted | Median | Full Range | watts/kg | 28 days |
|
|
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| 5 |
| 6 |
| EG001 | Cohort 1 - Comparator | RT001 comparator, oral, 2 capsules/day RT001 comparator: RT001 comparator is encapsulated non-deuterated linoleic acid ethyl ester. | 0 | 3 | 0 | 3 | 2 | 3 |
| EG002 | Cohort 2 - RT001 (9 g/Day) | RT001, oral, 10 capsules/day RT001: RT001 is encapsulated di-deutero synthetic homologue of linoleic acid ethyl ester. Each capsule contains 900 mg of RT001. | 0 | 7 | 1 | 7 | 5 | 7 |
| EG003 | Cohort 2 - Comparator | RT001 comparator, oral, 10 capsules/day RT001 comparator: RT001 comparator is encapsulated non-deuterated linoleic acid ethyl ester. | 0 | 3 | 0 | 3 | 2 | 3 |
|
|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
|
| Abdominal distension | Gastrointestinal disorders |
|
| abdominal pain | Gastrointestinal disorders | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Conjunctivitis | Infections and infestations | Systematic Assessment |
|
| sinusitis | Infections and infestations | Systematic Assessment |
|
| dysgeusia | Nervous system disorders | Systematic Assessment |
|
| facial fracture | Injury, poisoning and procedural complications | Systematic Assessment |
|
| muscle strain | Injury, poisoning and procedural complications | Systematic Assessment |
|
| palpitations | Cardiac disorders | Systematic Assessment |
|
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| D009422 | Nervous System Diseases |
| D013118 | Spinal Cord Diseases |
| D020271 | Heredodegenerative Disorders, Nervous System |
| D019636 | Neurodegenerative Diseases |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D028361 | Mitochondrial Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D017531 | Health Care Evaluation Mechanisms |
| D011787 | Quality of Health Care |
| D017530 | Health Care Quality, Access, and Evaluation |
| D011634 | Public Health |
| D004778 | Environment and Public Health |