A PHASE 2 STUDY OF THE SAFETY AND EFFICACY OF RTA 408 IN PATIENTS WITH MITOCHONDRIAL MYOPATHY
- Conditions
- Mitochondrial myopathy as evidenced by the following 2 criteria (must meet both):a. Have a history of exercise intolerance with or without weakness and/or progressive exercise intolerance (in which modest exercise typically provokes heaviness, weakness, aching of active muscles, or tachycardia).b. Have a known primary mitochondrial DNA mutation of a nuclear DNA defect that is associated with reduced activity of at least 1 mitochondrially encoded respiratory chain complexMedDRA version: 18.0Level: PTClassification code 10027710Term: Mitochondrial myopathySystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
- Registration Number
- EUCTR2014-003501-15-DK
- Lead Sponsor
- Reata Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 52
Patients must:
1. Have mitochondrial myopathy as evidenced by the following 2 criteria (must meet both):
a. Have a history of exercise intolerance with or without weakness and/or progressive exercise intolerance (in which modest exercise typically provokes heaviness, weakness, aching of active muscles, or tachycardia)
b. Have a known primary mitochondrial DNA mutation or a nuclear DNA defect that is associated with reduced activity of at least 1 mitochondrially encoded respiratory chain complex
2. Be male or female and =18 years of age and =75 years of age
3. Have no changes to their exercise regimen within 30 days prior to Study Day 1 and be willing to remain on the same exercise regimen during the 16-week study period
4. Have the ability to complete maximal exercise testing
5. Have peak work during maximal exercise testing of =1.5 W/kg
6. Have adequate kidney function defined as an estimated glomerular filtration rate (eGFR) =60 mL/min/1.73 m2 using the Modification of Diet in Renal Disease (MDRD) 4-variable formula
7. Be able to swallow capsules
8. Be willing and able to cooperate with all aspects of the protocol
9. Be willing to practice the medically acceptable methods of birth control
10. Provide written informed consent for study participation, approved by the appropriate Institutional Review Board
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 51
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1
Patients must not:
1. Have uncontrolled diabetes (HbA1c >11.0%)
2. Have B-type natriuretic peptide level >200 pg/mL
3. Have a history of clinically significant left-sided heart disease and/or clinically significant cardiac disease, including but not limited to any of the following:
a. Clinically significant congenital or acquired valvular disease
b. Pericardial constriction (based on echocardiogram performed at Screening Visit or within 30 days prior to Screening Visit)
c. Restrictive or congestive cardiomyopathy (based on echocardiogram performed at Screening Visit or within 30 days prior to Screening Visit)
d. Symptomatic coronary disease (prior myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or angina)
e. Evidence of left ventricular diastolic dysfunction
f. History of atrial fibrillation
g. History of unstable arrhythmias
h. Cardiac insufficiency, defined as New York Heart Association Class >2
4. Have known active fungal, bacterial, and/or viral infection, including human immunodeficiency virus or hepatitis virus (B or C)
5. Have known or suspected active drug or alcohol abuse, as per investigator judgment
6. Have clinically significant abnormalities of clinical hematology or biochemistry, including but not limited to elevations greater than 1.5 times the upper limit of normal of aspartate aminotransferase, alanine aminotransferase or creatinine. Levels above this threshold are allowable if attributable to muscle injury.
7. Have any abnormal laboratory test value or clinically significant pre-existing medical condition that, in the opinion of the investigator, would put the patient at risk by study enrollment
8. Have taken any of the following drugs within 7 days prior to Study Day 1 or plan to take any of these drugs during the time of study participation:
a. Sensitive substrates for cytochrome P450 2C8 or 3A4 (e.g., repaglinide, midazolam, sildenafil)
b. Moderate or strong inhibitors or inducers of cytochrome P450 3A4 (e.g., carbamazepine, phenytoin, ciprofloxacin, grapefruit juice)
c. Substrates for p-glycoprotein transporter (e.g., ambrisentan, digoxin)
9. Have a history of clinically significant liver disease (e.g., fibrosis, cirrhosis, hepatitis), or has, at screening, clinically relevant deviations in laboratory tests including any one of the following:
a. alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 1.5-fold ULN,
b. bilirubin > 1.2-fold ULN,
c. alkaline phosphatase (ALP) > 2-fold ULN,
d. kidney insufficiency as defined by creatinine level > 1.5 mg/dL,
e. albumin < lower limit of normal (LLN)
10. Have participated in any other interventional clinical study within 30 days prior to Study Day 1
11. Have a cognitive impairment that may preclude ability to comply with study procedures
12. 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
13. Have used antioxidant supplements, including but not limited to idebenone, coenzyme Q10, nicotinamide, and vitamin E above the recommended daily allowance, within 14 days prior to Study Day 1 or plan to take any of these supplements during the time of study participation
14. Have taken chronic treatment with corticosteroids within 30 days prior to Study Day 1
15. Have had significant suicidal ideation within 1 month prior
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method