A single-center, open-label study to evaluate the absorption, distribution, metabolism, and excretion (ADME) and pharmacokinetics of LMI070 (branaplam) following a single oral dose of 140 mg [14C]branaplam in healthy male participants
- Conditions
- Spinal muscular atrophy (SMA) and Huntingtons disease10029317
- Registration Number
- NL-OMON50950
- Lead Sponsor
- ovartis
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 6
1. Signed informed consent must be obtained prior to participation in the study.
2. Healthy male participants age 30 to 54 years, both inclusive.
3. In good health as determined by medical history, physical examination, vital
signs, ECG, and laboratory tests at screening.
4. Laboratory values within the reference range at the local laboratory, unless
deemed not clinically significant by the investigator or designee.
5. Sexually active male participants must agree to use a condom during
intercourse for the entire study duration and for up to 90 days after dosing,
and should not father a child in this period. A condom is required to be used
also by vasectomized men to prevent delivery of the drug via seminal fluid.
For complete overview see the protocol
1. Use of other investigational drugs within 5 half-lives of initiation of
study treatment (if known), or within 6 months prior to admission (in case of
therapeutics with expected long half-lives such as immunoglobulin [Ig]G
antibodies), or within 30 days after dosing (for small-molecule drugs with
daily dosing scheme), or longer if required by local regulations.
The investigator is expected to apply the appropriate due diligence
(considering available information in public, IBs, and/or patient information)
to ensure that the washout times detailed above are sufficient to avoid a
carry-over of PK or PD or have an impact on participant safety by the other
investigational drug.
2. Evidence of any remaining PD effects not having yet returned to baseline
after previous exposure to an investigational drug (in the judgment of the
investigator).
3. Absence of regular defecation pattern (participants with a mean defecation
frequency of less than on average once per 2 days or chronic diarrhea).
4. Any surgical or medical condition that might significantly alter the ADME of
drugs, or which may jeopardize the participant in case of participation in the
study. The investigator should make this determination in consideration of the
participant*s medical history and/or clinical or laboratory evidence of any of
the following at screening or baseline:
• Inflammatory bowel disease, peptic ulcers, GI including rectal bleeding.
• Major GI tract surgery such as gastrectomy, gastroenterostomy, or bowel
resection.
• Pancreatic injury or pancreatitis.
• Liver disease or liver injury as indicated by abnormal liver function tests.
Alanine aminotransferase (ALT); serum glutamic pyruvic transaminase, aspartate
aminotransferase (AST); serum glutamic oxaloacetic transaminase, gamma-glutamyl
transferase (GGT); alkaline phosphatase (ALP); and serum bilirubin will be
tested.
• History or presence of impaired renal function as indicated by clinically
significantly abnormal creatinine or blood urea nitrogen (BUN) and/or urea
values, abnormal urinary constituents (e.g., albuminuria).
• Evidence of urinary obstruction or difficulty in voiding.
5. History of drug abuse or harmful alcohol use within the 12 months prior to
dosing, or evidence of such abuse as indicated by the laboratory assays
conducted during screening and baseline. Harmful alcohol use is defined as a
history of, or current alcohol misuse/abuse, defined as *exceeding 21
units/week (''units* generally contain between 8 and 14 grams of pure ethanol).
For complete overview see the protocol
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>- To characterize the plasma pharmacokinetics (PK) of branaplam and its<br /><br>metabolite UFB112.<br /><br>- To determine the PK of total radiolabeled components in blood and plasma.<br /><br>- To determine the rates and routes of excretion of total radiolabeled<br /><br>components, including mass balance of total radiolabeled components in urine<br /><br>and feces following a single 140-mg dose of [14C]branaplam in healthy male<br /><br>participants.</p><br>
- Secondary Outcome Measures
Name Time Method <p>To assess the safety and tolerability of a single 140-mg oral dose of<br /><br>[14C]branaplam administered to healthy male participants. </p><br>