safety, tolerability, efficacy of mtp-131 for treatment of mitochondrial disease in subjects from the mmpower study

Conditions: Primary Mitochondrial Disease

Summary: this randomized, double-blind, placebo-controlled, crossover study screened 32 subjects with primary mitochondrial myopathy (pmm) to evaluate the safety, tolerability, pharmacokinetics (pk), and efficacy of subcutaneous elamipretide in this patient population.

this randomized, double-blind, placebo-controlled, crossover study screened 32 subjects with primary mitochondrial myopathy (pmm) who had completed participation in the spimm-201 study where they had received 5 days of intravenous (iv) elamipretide (0.01, 0.10, or 0.25 mg/kg/hour infused for 2 hours) or placebo (randomized 3:1). the primary objective was to evaluate the effect of single daily subcutaneous (sc) doses of elamipretide administered for 4 weeks on the 6-minute walking distance (6mwd). subjects were randomized (1:1) to one of two sequence groups: 4-weeks of treatment with 40 mg elamipretide administered once daily sc in treatment period 1 followed by 4-weeks of treatment with placebo administered once daily sc in treatment period 2 (separated by a 4-week washout period), or vice versa. each sequence group went through 5 distinct periods: screening, treatment period 1, washout, treatment period 2, and follow-up. safety, tolerability, pharmacokinetics (pk), and efficacy of subcutaneous elamipretide in this patient population were analyzed.

Eligibility criteria:
inclusion criteria: * subject completed participation in the spimm-201 study without a significant protocol deviation that would suggest the subject may not be able to complete all study requirements in the opinion of the sponsor * subject must reside in north america for the duration of the study * subject has not received study drug in the spimm-201 study within 3 weeks prior to screening * women of childbearing potential must agree to use 1 of the methods of birth control specified in the protocol from the date they sign the informed consent form (icf) until two months after the last dose of study drug * subject has been on stable (unchanged and constant) medications (including over-the counter treatments, vitamins, or supplements) for at least 1 month prior to the baseline visit exclusion criteria: * subject has any prior or current medical condition that, in the judgment of the investigator, would prevent the subject from safely participating in and/or completing all study requirements (i.e. unstable angina or recent myocardial infarction) * subject has received any investigational compound and/or has participated in another interventional clinical study within 30 days prior to the baseline visit or is concurrently enrolled in any non-interventional research of any type judged to be scientifically or medically incompatible with the study as deemed by the investigator in consultation with the sponsor * subject experienced an adverse reaction to study drug in the spimm-201 study that contraindicates further treatment with elamipretide in the opinion of the investigator and/or sponsor * female subjects who are pregnant, planning to become pregnant, or lactating * subject has undergone an in-patient hospitalization within the 1 month prior to the screening visit or is likely to need in-patient hospitalization or a surgical procedure during the course of the study * subject has a creatinine clearance ≤30 ml/min as calculated by the cockcroft gault equation * subject has a corrected qt interval (qtc) elongation defined as a qtc \>450 msec in male subjects and \>480msec in female subjects. note: at the initial electrocardiogram (ecg), if qtc exceeds these parameters, the ecg may be repeated 2 more times, and the average of the 3 qtc values used to determine the subjects eligibility * subject has uncontrolled hypertension in the judgment of the investigator (e.g. elevated above \>160 mmhg systolic or \>100 mmhg diastolic despite appropriate treatment on two consecutive readings) * subject has a history of clinically significant hypersensitivity or allergy to any of the excipients contained in the study drug * subject has a history of active alcoholism or drug addiction during the year before the screening visit

Keywords: primary mitochondrial disease mitochondrial myopathy elamipretide mtp-131 bendavia™