A Clinical Study to Evaluate the Efficacy and Safety of MIN-102 (IMP) in Male AMN Patients

In Part 1 of the study, eligible patients were randomized in a 2:1 ratio to receive leriglitazone or placebo. For patients randomized to leriglitazone, dosing was adjusted on an individual-patient basis to achieve the target plasma leriglitazone exposure, with a maximum allowed range of ±20%. Patients randomized to placebo received the same amount of a matched placebo suspension. Blood samples to determine leriglitazone plasma concentrations were obtained at all visits after the baseline visit (V0). Dose-adjustment recommendations were made by a pharmacokinetic (PK) expert from the central laboratory who was unblinded to PK data. For patients not tolerating the target plasma exposure, the investigator could reduce the study medication dose at any timepoint by up to 50%. To preserve the blind, random dose adjustments were made for the patients receiving placebo. Part 2 was an open-label treatment extension study which started immediately after the day of last treatment in Part 1 at V6, which, after 96 weeks of double-blind treatment in Part 1, was simultaneously the baseline visit of Part 2 of the study. All patients in Part 2 (including those randomized to placebo in Part 1) received a leriglitazone dose to achieve the predefined target plasma exposure. All patients who were taking doses of ≤ the starting dose in Part 1 at the end of Part 1 (V6) started Part 2 with the same dose. All other patients reverted to the Part 1 starting dose of leriglitazone oral suspension. Patients and investigators were advised that dose adjustments could occur in both groups, those previously assigned to leriglitazone and to placebo, since patients who were on a stable leriglitazone dose during Part 1 may no longer have been at their optimum exposure level at Week 96. After the potential adjustment informed by PK results obtained at 100 weeks (V7) and 108 weeks (V8), the study medication dosage could not otherwise be changed except if required for safety/tolerability reasons. Downwards adjustments of the dose in this case could be introduced, but the minimum exposure had to be achieved. Patients who experienced study medication-related AEs and who could not tolerate the study medication, even at the minimum permitted exposure level, were discontinued from the study. In Part 2 patients were evaluated with 144 weeks of daily administration of study medication and periodic on-site visits and follow-up phone calls. After 144 weeks of daily administration in Part 2, regular visits and safety visits or follow-up phone calls were to each take place at 6-month intervals for an unlimited time until either: (1) the patient withdrew consent; (2) significant safety or tolerability issues appeared and/or the patient's general health status, in the clinical judgment of the investigator, declined to an extent that the risks of treatment with leriglitazone outweighed the potential benefits; (3) the patient underwent hematopoietic stem-cell transplantation; (4) leriglitazone received marketing authorization for the treatment of AMN; or (5) Minoryx Therapeutics decided to terminate this study, whichever of these events occurred first.