protein aggregation and protein misfolding diseases (lysosomal storage diseases and neuromuscular disorders such as ALS protein aggregation and protein misfolding diseases (lysosomal storage diseases and neuromuscular disorders such as ALS
Conditions
Interventions
Thirty-two (32) subjects will be randomised to ensure 26 evaluable subjects per
group. Subjects participating in the trial will attend the clinical trial site
for screening, 4 in-house periods (Trea
Sponsors
Orphazyme A/S
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. The subject is able to read and understand the Subject Information Sheet and Informed Consent Form. 2. The subject has signed the trial-specific Informed Consent Form. 3. The subject is a man 4. The subject must: a. remain sexually abstinent, when this is in line with his preferred and usual lifestyle OR b. engage exclusively in same-sex relationships OR c. agree to avoid impregnating his partner from the Screening Visit until 2 weeks after the last dose of IMP, AND d. agree to use highly effective contraception methods as described in Appendix 4 from the Screening Visit until 2 weeks after dosing if his female partner is of childbearing potential e. not donate sperm until *3 months after the last dose of IMP
Exclusion criteria
Exclusion criteria: 1. The subject has taken any prescription or non-prescription medication 21 units per week, or substance use (excluding nicotine or caffeine) deemed significant by the investigator, or a history of substance abuse (DSM-5® criteria)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Endpoint: * Placebo-corrected change-from-baseline QTcF (**QTcF). Pharmacokinetic Endpoints: The pharmacokinetic parameters calculated for arimoclomol, M2 and M105 in plasma are: * AUC0-inf: area under the arimoclomol, M2 and M105 plasma-concentration-time curves from zero to infinity * AUC0-t: area under the arimoclomol, M2 and M105 plasma-concentration-time curves from zero to last quantifiable plasma concentration * AUC0-8: area under the arimoclomol, M2 and M105 plasma-concentration-time curves from zero to 8 hours post-dose (Day 1 only) * AUC%extrap: percent extrapolated of total AUC0-inf * Cmax: maximum observed plasma concentration of arimoclomol, M2 and M105 * Tmax: time at which maximum observed plasma concentrations of arimoclomol, M2 and M105 occurred (Day 1 only) * t*: terminal elimination half-life for arimoclomol, M2 and M105 * CL/F (oral clearance) (for arimoclomol only) * Vz/F: apparent volume of distribution for arimoclomol * MR (metabolic ratio, defined as AUCmetabolite/AUCarimoclomol) Safety Endpoints: * Adverse events * Absolute values and changes from baseline in clinical safety laboratory test values, vital signs, weight, and ECG parameter values * Potentially clinically significant (PCS) clinical safety laboratory test values, vital signs, weight changes, and ECG parameter values | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Endpoints: * Change-from-baseline QTcF, HR, PR, QRS intervals (*QTcF, *HR, *PR, and *QRS) * Placebo-corrected change-from-baseline HR, PR, and QRS (**HR, **PR, **QRS) * Categorical outliers for QTcF, HR, PR, and QRS * Frequency of treatment-emergent changes of T-wave morphology and U-waves presence | — |
Countries
Netherlands
Outcome results
None listed