Targeting Metabolic Flexibility in ALS (MetFlex); Safety and Tolerability of Trimetazidine for the Treatment of ALS

MetFlex

MetFlex is an investigator led, open-label, single-arm, Phase 2a trial to determine the safety and tolerability of trimetazidine for the treatment of amyotrophic lateral sclerosis/motor neuron disease (ALS/MND).

2021-06-29

2023-05-24

2023-05-24

Completed

Early phase I

21

Inclusion Criteria: * Age between 18 and 75 years * Signed informed consent prior to the initiation of any study-specific procedures * Familial or sporadic ALS/MND, defined as clinically possible, probable, or definite as per the El Escorial criteria * Relative TRICALS risk score between -6.0 to -2.0 (75% of patients with ALS/MND) * Metabolic index ≥110%, at the screening visit. * The use of riluzole will be permitted during the study. Individuals taking riluzole must be on a stable dose for at least 30 days prior to the baseline visit, or stopped taking riluzole at least 30 days prior to the baseline visit. * Ability to swallow tablets * Able to lie with torso elevated at a 35° angle for 30 minutes without respiratory support * Able to give informed consent (as judged by the investigator) and able to comply with all study visits and all study procedures * Females must not be able to become pregnant (e.g. post-menopausal, surgically sterile or using highly effective birth control methods) for the duration of the study. Highly effective methods of birth control are those with a failure rate of \< 1% per year when employed consistently and correctly, e.g. Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: * oral * intravaginal * transdermal * Progestogen-only hormonal contraception associated with inhibition of ovulation: * oral * injectable * implantable * intrauterine device (IUD) * intrauterine hormone-releasing system ( IUS) * vasectomised partner * Females of child-bearing potential must have a negative serum pregnancy test at screening and baseline and be non-lactating Exclusion Criteria: * Unable to provide informed consent * History of, or current diagnosis of diabetes or medical condition that impacts whole body energy expenditure (e.g. Hashimoto's, heart disease) * Parkinson's disease or parkinsonism, tremor, restless-leg syndrome * Safety Laboratory Criteria at screening related to significant kidney disease: * Creatinine clearance \< 50 mL / min (Cockcroft-Gault) based on Cystatin C * Tracheostomy or non-invasive ventilation (NIV) use \> 22 hours per day * Inability to swallow tablets * Contraindication therapy: * Allergy for one of the product's active pharmaceutical ingredients (APIs) or excipients. * Antihypertensive treatment \[Trimetazidine may cause hypotension\] * Evidence of malignant disease * Significant neuromuscular disease other than ALS/MND * Ongoing disease that may cause neuropathy * Pregnancy or breastfeeding * Females actively seeking to become pregnant who are not using an adequate form of contraceptive as detailed in the Inclusion criteria. * Deprivation of freedom by administrative or court order

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': 'Open-label, single-arm study without placebo', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 21, 'type': 'ACTUAL'}}

2023-07-20