A Study of Omaveloxolone in Children With Friedreich's Ataxia
Study Details
Study Description
Brief Summary
This is an open-label study evaluating the safety, tolerability, and PK following single-dose administration of omaveloxolone in pediatric patients with FA. The study will consist of 3 parts (Parts A, B, and C) based on age.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Part A - Cohort 1 Part A - Cohort 1 will contain patients ≥12 to <16 years of age. Patients will receive a single oral dose of 150 mg omaveloxolone. |
Drug: Omaveloxolone
One dose of omaveloxolone will be taken orally. Dosage to be determined based on age and PK data from prior Parts.
Other Names:
|
| Experimental: Part A - Cohort 2 Part A - Cohort 2 will contain patients ≥12 to <16 years of age. Patients will receive a single oral dose of omaveloxolone at a dosage level determined by a Bayesian population pharmacokinetic (popPK) analysis using the data from Part A - Cohort 1 to select the dose. |
Drug: Omaveloxolone
One dose of omaveloxolone will be taken orally. Dosage to be determined based on age and PK data from prior Parts.
Other Names:
|
| Experimental: Part B Part B will contain patients ≥6 to <12 years of age and will initiate in parallel with Part A - Cohort 2. Patients will receive a single oral dose of omaveloxolone at a dosage level determined by a Bayesian population pharmacokinetic (popPK) analysis using the data from Part A - Cohort 1 to select the dose. |
Drug: Omaveloxolone
One dose of omaveloxolone will be taken orally. Dosage to be determined based on age and PK data from prior Parts.
Other Names:
|
| Experimental: Part C Part C will contain patients ≥2 to <6 years of age. Subjects will receive a single oral dose of omaveloxolone at a dosage level determined by a Bayesian population pharmacokinetic (popPK) analysis using the data from Part A and Part B to select the dose. |
Drug: Omaveloxolone
One dose of omaveloxolone will be taken orally. Dosage to be determined based on age and PK data from prior Parts.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Apparent clearance (CL/F) of omaveloxolone [Predose (0 hour), after dose 1 hour, 2 hours, 3 hours, 4 hours, 24 hours, and 96 hours]
Blood samples to assess omaveloxolone PK will be collected predose and at the specified time points. Bayesian popPK analyses will be conducted after the completion of dosing for Part A Cohort 1 and after completion of dosing for each age cohort (Part A, Part B, Part C).
- Maximum concentration (Cmax) of omaveloxolone [Predose (0 hour), after dose 1 hour, 2 hours, 3 hours, 4 hours, 24 hours, and 96 hours]
Blood samples to assess omaveloxolone PK will be collected predose and at the specified time points. Bayesian popPK analyses will be conducted after the completion of dosing for Part A Cohort 1 and after completion of dosing for each age cohort (Part A, Part B, Part C).
- Volume of distribution (V/F) of omaveloxolone [Predose (0 hour), after dose 1 hour, 2 hours, 3 hours, 4 hours, 24 hours, and 96 hours]
Blood samples to assess omaveloxolone PK will be collected predose and at the specified time points. Bayesian popPK analyses will be conducted after the completion of dosing for Part A Cohort 1 and after completion of dosing for each age cohort (Part A, Part B, Part C).
- Area under the plasma concentration-time curve from 0 extrapolated to infinity (AUC0-∞) of omaveloxolone [Predose (0 hour), after dose 1 hour, 2 hours, 3 hours, 4 hours, 24 hours, and 96 hours]
Blood samples to assess omaveloxolone PK will be collected predose and at the specified time points. Bayesian popPK analyses will be conducted after the completion of dosing for Part A Cohort 1 and after completion of dosing for each age cohort (Part A, Part B, Part C).
- Area under the plasma concentration-time curve from 0 to tlast (AUC0-tlas) of omaveloxolone [Predose (0 hour), after dose 1 hour, 2 hours, 3 hours, 4 hours, 24 hours, and 96 hours]
Blood samples to assess omaveloxolone PK will be collected predose and at the specified time points. Bayesian popPK analyses will be conducted after the completion of dosing for Part A Cohort 1 and after completion of dosing for each age cohort (Part A, Part B, Part C).
- Area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24) of omaveloxolone [Predose (0 hour), after dose 1 hour, 2 hours, 3 hours, 4 hours, 24 hours, and 96 hours]
Blood samples to assess omaveloxolone PK will be collected predose and at the specified time points. Bayesian popPK analyses will be conducted after the completion of dosing for Part A Cohort 1 and after completion of dosing for each age cohort (Part A, Part B, Part C).
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Have genetically confirmed FA.
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Be male or female and ≥2 years of age and <16 years of age.
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Have a left ventricular ejection fraction ≥ 40% (based on echocardiogram [ECHO] performed at Screening Visit).
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Be willing and able to cooperate with all aspects of the protocol.
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During screening, during the treatment period, and until 28 days following administration of the single dose of omaveloxolone, females of childbearing potential must practice at least 1 of the acceptable methods of birth control described in Section 6.9.
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During screening, during the treatment period, and until 28 days after the single dose of omaveloxolone, fertile males who have female partners of childbearing potential must practice one of the acceptable methods of birth control described in Section 6.9.
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Females of childbearing potential must have negative results for pregnancy tests at screening, based on a serum negative sample obtained prior to study drug administration.
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Parent or guardian willing to provide consent and patients ≥6 years of age willing to provide an assent form. Emancipated minor patients can provide consent.
Exclusion Criteria:
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Have uncontrolled diabetes (HbA1c >11.0%).
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Have B-type natriuretic peptide (BNP) level >200 pg/mL at screening.
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Have a history of clinically significant (CS) left-sided heart disease and/or CS cardiac disease, with the exception of mild to moderate cardiomyopathy associated with FA.
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Presence of outflow tract obstruction defined as a peak instantaneous gradient >50 mmHg (based off ECHO performed at screening).
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Have a known active fungal, bacterial, and/or viral infection, including HIV or hepatitis (B or C).
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Have known or suspected active drug, nicotine use, or alcohol abuse, as per investigator judgment.
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Have any abnormal laboratory test value or CS pre-existing medical condition that, in the opinion of the investigator, would put the patient at risk by study participation.
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Have taken any moderate or strong inhibitors and/or inducers of cytochrome P450 3A4 within the 7 days prior to Day 1 or plan to take during study participation (eg, itraconazole, carbamazepine, phenytoin, ciprofloxacin, grapefruit juice,cannabidiol, fluconazole, fluvoxamine, verapamil, diltiazem).
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Have a history of CS liver disease (eg, fibrosis, cirrhosis, hepatitis), or have clinically relevant deviations in laboratory tests at screening
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Plan to or have participated in any other interventional clinical study within the 30 days prior to Day 1.
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Have a cognitive impairment that may preclude ability to comply with study procedures, in the opinion of the investigator.
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Be unable to comply with the requirements of the study protocol or be unsuitable for the study for any reason, in the opinion of the investigator.
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Have previously documented mitochondrial respiratory chain disease.
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Have a history of thromboembolic events within the past 5 years.
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Plan to or have taken anticoagulant therapy within 30 days prior to Day 1 with the exception of a daily low dose aspirin (up to 81 mg).
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Plan to or have scheduled surgical treatment for scoliosis or foot deformity during the study.
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Have had significant suicidal ideation within 30 days prior to Screening Visit, as per investigator judgment, or any history of suicide attempt.
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For females, be pregnant or breastfeeding.
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Positive test result for COVID-19 at screening.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | United States | 19104 |
Sponsors and Collaborators
- Reata Pharmaceuticals, Inc.
Investigators
- Principal Investigator: David Lynch, MD, Children's Hospital of Philadelphia
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 408-C-2001