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A First in Human Study of RT001 in Patients With Friedreich's Ataxia

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ClinicalTrials.gov Identifier: NCT02445794
Recruitment Status : Completed
First Posted : May 15, 2015
Results First Posted : November 27, 2020
Last Update Posted : November 27, 2020
Sponsor:
Information provided by (Responsible Party):
Retrotope, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Friedreich's Ataxia
Interventions Drug: Low dose cohort
Drug: High dose cohort
Enrollment 19
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Cohort 1 - RT001 (1.8 g/Day) Cohort 1 - Comparator Cohort 2 - RT001 (9 g/Day) Cohort 2 - Comparator
Hide Arm/Group Description

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.

RT001 comparator, oral, 2 capsules/day

RT001 comparator: RT001 comparator is encapsulated non-deuterated linoleic acid ethyl ester.

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.

RT001 comparator, oral, 10 capsules/day

RT001 comparator: RT001 comparator is encapsulated non-deuterated linoleic acid ethyl ester.

Period Title: Overall Study
Started 6 3 7 3
Completed 6 3 5 3
Not Completed 0 0 2 0
Reason Not Completed
Adverse Event             0             0             2             0
Arm/Group Title Cohort 1 - RT001 Cohort 1 - Comparator Cohort 2 - RT001 Cohort 2 - Comparator Total
Hide Arm/Group Description RT001 - 2 capsules/day (1.8 g/day) RT001 comparator - 2 capsules/day RT001 - 10 capsules/day (9 g/day) RT001 comparator - 10 capsules/day Total of all reporting groups
Overall Number of Baseline Participants 6 3 7 3 19
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 6 participants 3 participants 7 participants 3 participants 19 participants
39.5  (7.61) 45.3  (2.08) 28.6  (7.46) 26.3  (4.16) 34.3  (9.47)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 6 participants 3 participants 7 participants 3 participants 19 participants
Female 3 1 5 1 10
Male 3 2 2 2 9
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 6 participants 3 participants 7 participants 3 participants 19 participants
White 6 3 7 3 19
American Indian or Alaska Native 0 0 1 0 1
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 6 participants 3 participants 7 participants 3 participants 19 participants
22.82  (3.857) 26.17  (2.798) 21.63  (3.096) 24.63  (7.931) 23.47  (4.128)
1.Primary Outcome
Title Number of Patients With Adverse Events
Hide Description [Not Specified]
Time Frame 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cohort 1 - RT001 (1.8 g/Day) Cohort 1 - Comparator Cohort 2 - RT001 (9 g/Day) Cohort 2 - Comparator
Hide Arm/Group Description:

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.

RT001 comparator, oral, 2 capsules/day

RT001 comparator: RT001 comparator is encapsulated non-deuterated linoleic acid ethyl ester.

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.

RT001 comparator, oral, 10 capsules/day

RT001 comparator: RT001 comparator is encapsulated non-deuterated linoleic acid ethyl ester.

Overall Number of Participants Analyzed 6 3 7 3
Measure Type: Number
Unit of Measure: participants
5 2 5 2
2.Secondary Outcome
Title Pharmacokinetics - Area Under the Concentration-time Curve After a Single Dose
Hide Description 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
Time Frame 24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title RT001, Oral, 1.8 g/Day RT001, Oral, 9 g/Day
Hide Arm/Group Description:

RT001, oral, 1.8 g QD for 28 days or matching comparator

RT001: RT001 is encapsulated di-deutero synthetic homologue of linoleic acid ethyl ester. Each capsule contains 900 mg of RT001.

RT001 comparator: RT001 comparator is encapsulated non-deuterated linoleic acid ethyl ester.

RT001, oral, 4.5 g BID for 28 days or matching comparator

RT001: RT001 is encapsulated di-deutero synthetic homologue of linoleic acid ethyl ester. Each capsule contains 900 mg of RT001.

RT001 comparator: RT001 comparator is encapsulated non-deuterated linoleic acid ethyl ester.

Overall Number of Participants Analyzed 6 7
Mean (Standard Deviation)
Unit of Measure: ug*h/mL
524  (86) 915  (251)
3.Secondary Outcome
Title Pharmacokinetics - Maximum Observed Plasma Concentration After a Single Dose
Hide Description 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
Time Frame 24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cohort 1 - RT001 (1.8 g/Day) Cohort 2 - RT001 (9 g/Day)
Hide Arm/Group Description:

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.

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.

Overall Number of Participants Analyzed 6 7
Mean (Standard Deviation)
Unit of Measure: ug/mL
35.9  (9.8) 58.6  (16)
4.Secondary Outcome
Title Pharmacokinetics - Time to Reach Maximum Plasma Concentration After a Single Dose
Hide Description TMax measured for the low and high dose cohorts
Time Frame 24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cohort 1 - RT001 (1.8 g/Day) Cohort 2 - RT001 (9 g/Day)
Hide Arm/Group Description:

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.

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.

Overall Number of Participants Analyzed 6 7
Mean (Standard Deviation)
Unit of Measure: h
6.05  (0) 8.0  (0)
5.Secondary Outcome
Title Pharmacokinetics - Maximum Observed Plasma Concentration After Final Dose on Day 28
Hide Description

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

Time Frame Day 28-Day 31 (3 days)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cohort 1 - RT001 (1.8 g/Day) Cohort 2 - RT001 (9 g/Day)
Hide Arm/Group Description:

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.

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.

Overall Number of Participants Analyzed 6 5
Mean (Standard Deviation)
Unit of Measure: ug/mL
91  (44.6) 359.9  (31.6)
6.Secondary Outcome
Title Pharmacokinetics - Terminal Half-life Estimation After Final Dose on Day 28
Hide Description

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

Time Frame Day 28-Day 31 (3 days)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cohort 1 - RT001 (1.8 g/Day) Cohort 2 - RT001 (9 g/Day)
Hide Arm/Group Description:

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.

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.

Overall Number of Participants Analyzed 6 5
Mean (Standard Deviation)
Unit of Measure: h
42.3  (9.77) 30.3  (18.3)
7.Secondary Outcome
Title Change From Baseline at 28 Days in the Timed 25 Foot Walk (T25FW)
Hide Description

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.

Time Frame 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cohort 1 - RT001 (1.8 g/Day) Cohort 1 - Comparator Cohort 2 - RT001 (9 g/Day) Cohort 2 - Comparator
Hide Arm/Group Description:

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.

RT001 comparator, oral, 2 capsules/day

RT001 comparator: RT001 comparator is encapsulated non-deuterated linoleic acid ethyl ester.

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.

RT001 comparator, oral, 10 capsules/day

RT001 comparator: RT001 comparator is encapsulated non-deuterated linoleic acid ethyl ester.

Overall Number of Participants Analyzed 6 3 6 3
Mean (Standard Deviation)
Unit of Measure: sec
.503  (3.7751) -1.87  (1.1653) -7.475  (28.6458) .608  (2.4182)
8.Secondary Outcome
Title Change From Baseline at 28 Days in the Friedreich Ataxia Rating Scale (FARS) - Neurological Score (Minimum Score 0, Maximum Score 125, Lower is Better)
Hide Description 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.
Time Frame 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Cohort 1 - RT001 (1.8 g/Day) Cohort 1 - Comparator Cohort 2 - RT001 (9 g/Day) Cohort 2 - Comparator
Hide Arm/Group Description:

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.

RT001 comparator, oral, 2 capsules/day

RT001 comparator: RT001 comparator is encapsulated non-deuterated linoleic acid ethyl ester.

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.

RT001 comparator, oral, 10 capsules/day

RT001 comparator: RT001 comparator is encapsulated non-deuterated linoleic acid ethyl ester.

Overall Number of Participants Analyzed 6 3 7 3
Mean (Standard Deviation)
Unit of Measure: units on a scale maximum 125
-6.22  (2.796) -6.47  (4.768) -3.3  (2.080) -2  (3.464)
9.Secondary Outcome
Title Change From Baseline at 28 Days in Peak Workload for the Treated Population vs. the Comparator Population
Hide Description 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.
Time Frame 28 days
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects unable to start or complete the test were excluded from analysis. Treatment and comparator cohorts were pooled to allow for statistical analysis.
Arm/Group Title RT001 Cohort 1 - Comparator
Hide Arm/Group Description:

RT001, oral (pooled 1.8 g/d + 9.0 g/d)

RT001: RT001 is encapsulated di-deutero synthetic homologue of linoleic acid ethyl ester. Each capsule contains 900 mg of RT001.

RT001 comparator, oral

RT001 comparator: RT001 comparator is encapsulated non-deuterated linoleic acid ethyl ester.

Overall Number of Participants Analyzed 10 6
Median (Full Range)
Unit of Measure: watts/kg
.08
(-.1 to .34)
-.08
(-.3 to 0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection RT001, Cohort 1 - Comparator
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .008
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cohort 1 - RT001 (1.8 g/Day) Cohort 1 - Comparator Cohort 2 - RT001 (9 g/Day) Cohort 2 - Comparator
Hide Arm/Group Description

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.

RT001 comparator, oral, 2 capsules/day

RT001 comparator: RT001 comparator is encapsulated non-deuterated linoleic acid ethyl ester.

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.

RT001 comparator, oral, 10 capsules/day

RT001 comparator: RT001 comparator is encapsulated non-deuterated linoleic acid ethyl ester.

All-Cause Mortality
Cohort 1 - RT001 (1.8 g/Day) Cohort 1 - Comparator Cohort 2 - RT001 (9 g/Day) Cohort 2 - Comparator
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/6 (0.00%)      0/3 (0.00%)      0/7 (0.00%)      0/3 (0.00%)    
Hide Serious Adverse Events
Cohort 1 - RT001 (1.8 g/Day) Cohort 1 - Comparator Cohort 2 - RT001 (9 g/Day) Cohort 2 - Comparator
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/6 (0.00%)      0/3 (0.00%)      1/7 (14.29%)      0/3 (0.00%)    
Gastrointestinal disorders         
Steatorrhea requiring overnight hospitalization  [1]  0/6 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  1 0/3 (0.00%) 
Indicates events were collected by systematic assessment
[1]
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.
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Cohort 1 - RT001 (1.8 g/Day) Cohort 1 - Comparator Cohort 2 - RT001 (9 g/Day) Cohort 2 - Comparator
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/6 (83.33%)      2/3 (66.67%)      5/7 (71.43%)      2/3 (66.67%)    
Cardiac disorders         
palpitations   0/6 (0.00%)  0 0/3 (0.00%)  0 0/7 (0.00%)  0 1/3 (33.33%)  1
Gastrointestinal disorders         
Abdominal discomfort  [1]  1/6 (16.67%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0
Diarrhea   0/6 (0.00%)  0 0/3 (0.00%)  0 4/7 (57.14%)  4 1/3 (33.33%)  1
Abdominal distension  1/6 (16.67%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0
abdominal pain   0/6 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/3 (0.00%) 
Constipation   0/6 (0.00%)  0 0/3 (0.00%)  0 1/7 (14.29%)  1 0/3 (0.00%)  0
Infections and infestations         
Conjunctivitis   0/6 (0.00%)  0 1/3 (33.33%)  1 0/7 (0.00%)  0 0/3 (0.00%)  0
sinusitis   1/6 (16.67%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0
Injury, poisoning and procedural complications         
facial fracture   1/6 (16.67%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0
muscle strain   0/6 (0.00%)  0 1/3 (33.33%)  1 0/7 (0.00%)  0 0/3 (0.00%)  0
Nervous system disorders         
dysgeusia   1/6 (16.67%)  1 0/3 (0.00%)  0 0/7 (0.00%)  0 0/3 (0.00%)  0
Indicates events were collected by systematic assessment
[1]
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.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Frederic Heerinckx/VP Clinical Operations
Organization: Retrotope, Inc
Phone: 650-437-0700 ext 109
EMail: frederic@retrotope.com
Layout table for additonal information
Responsible Party: Retrotope, Inc.
ClinicalTrials.gov Identifier: NCT02445794    
Other Study ID Numbers: RT001-002
First Submitted: May 6, 2015
First Posted: May 15, 2015
Results First Submitted: August 19, 2020
Results First Posted: November 27, 2020
Last Update Posted: November 27, 2020