Single Dose Study of [14C]-IDV184001AN ([14C]-IDV184001) in Healthy Adult Male Participants

Study Overview
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Brief Summary
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The purpose of this open label study is to characterise the absorption, metabolism, excretion, and mass balance of [14C]-IDV184001AN ([14C]-IDV184001) in healthy adult male participants.

Detailed Description
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The study is designed as an open label, single-dose study in healthy adult participants for the following reasons: Oral administration of IDV184001AN has demonstrated linear PK and thus [14C]IDV184001AN will be given as a single dose. A comparator is not necessary for the evaluation of the objectives. Blinding of the study treatment is not required as there is no comparator. Conducting the study in healthy participants mitigates the potential confounding effects of the disease state and concomitant medications.

Official Title
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A Phase I, Open Label Study to Assess the Absorption, Metabolism, Excretion, and Mass Balance of a Single Dose of Oral [14C]-IDV184001AN in Healthy Adult Male Participants

Conditions
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Opioid Use Disorder

Intervention / Treatment
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* Drug: [14C]IDV184001AN


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants are eligible to be included in the study only if all of the following criteria apply: Participant must be 19 to 55 years of age inclusive, at the time of signing the informed consent. Participant must have body weight of a minimum of 50.0 kg at the Screening Visit and body mass index within the range 18.0 to 32.0 kg/m2 (inclusive). Participant must be male and who is healthy as determined by medical evaluation. Participant agrees to follow contraception guidelines from the time of dosing of study drug until at least 90 days after dosing of study drug. This includes use of highly effective contraception if sexually active with a non-pregnant partner of child-bearing potential, and agreement not to donate sperm from dosing until at least 90 days post-dose. There are no restrictions for a vasectomised male provided his vasectomy has been performed 4 months or more prior to dosing. Participant must be continuous non smoker who has not used nicotine and tobacco containing products for at least 3 months prior to dosing based on participant self-reporting. Participant must be capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and compliance with contraception guidelines. Exclusion Criteria: Participants are excluded from the study if any of the following criteria apply: Have an ongoing medical history of clinically significant neurological, cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease, psychiatric or other disorder as judged by an Investigator that could potentially affect the study outcomes or compromise participant safety. Have clinically significant abnormal biochemistry, haematology or urinalysis results as judged by an Investigator. Have a history of narcolepsy or sleep apnea. Have disorders that may interfere with drug absorption, distribution, metabolism and excretion processes. Current active hepatic or biliary disease. Participants with cholecystectomy <90 days prior to the Screening Visit. Positive test results for HIV-1/HIV-2 antibodies, HBsAg or Hepatitis C antibodies at the Screening Visit. Have a blood pressure reading outside of the following range: Systolic <86 or >149 mmHg; Diastolic <50 or >94 mmHg at the Screening Visit. Serious cardiac illness or other medical condition including, but not limited to: Uncontrolled arrhythmias History of congestive heart failure QTcF >450 msec or history of prolonged QT syndrome Myocardial infarction Uncontrolled symptomatic angina History of suicidal ideation within 30 days prior to providing written informed consent as evidenced by answering yes' to questions 4 or 5 on the suicidal ideation portion of the C-SSRS completed at the Screening Visit or history of a suicide attempt (per the C-SSRS) in the 6 months prior to informed consent. Healthy participants who are taking, or have taken, any prescribed or over the counter drugs (other than 2 grams of acetaminophen per 24-hour period as of Day 1 or thyroid hormone replacement therapy) or herbal remedies in the 14 days or 5 half-lives (whichever is longer) prior to dosing of study drug. Treatment with any known drugs that are moderate or strong inhibitors/inducers of CYP3A4 or CYP2C19, including St. John's Wort, within 30 days prior to dosing of study drug. Any consumption of food or drink containing poppy seeds, grapefruit or Seville oranges within 14 days prior to dosing of study drug. Regular alcohol consumption >21 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine). Positive test result for alcohol and/or drugs of abuse at the Screening Visit or at check-in. Concurrent treatment or treatment with an investigational drug or device within 30 days or 5 half-lives (whichever is longer) prior to dosing of study drug. Blood donation of approximately 500 mL or more within 56 days or plasma donation within 7 days prior to the Screening Visit. Known hypersensitivity to INDV-2000. Has less than 1 bowel movement every 2 days. Recent history of abnormal bowel movements, such as diarrhea, loose stools or constipation, within 2 weeks prior to dosing of study drug. Has received radiolabelled substances or has been exposed to radiation sources over the past 12 months or is likely to receive radiation exposure or radioisotopes within the next 12 months such that participation in this study would increase their total exposure beyond the recommended levels considered safe (ie, weighted annual limit recommended by the FDA 21CFR361 of 3000 mrem; FDA 2023). Site staff and/or participants who have a financial interest in, or an immediate family member of either the site staff and/or Indivior employees, directly involved in the study. Major surgical procedure (as defined by the Investigator) within 90 days prior to dosing of study drug or still recovering from prior surgery. Concurrent enrolment in another clinical study, unless it is an observational study. Participants who are unable, in the opinion of the Investigator, to comply fully with the study requirements. Any condition that, in the opinion of the Investigator or Indivior, would interfere with evaluation of the study drug or interpretation of participant safety or study results.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>[14C]IDV184001AN | Drug: [14C]IDV184001AN<br>* [14C]-IDV184001AN 200 mg/ 100 µCi/ 15 g oral suspension<br>* Other names: [14C]-IDV184001;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigation of the route(s) of elimination and the overall mass balance of IDV184001, following a single oral dose of [14C] IDV184001AN in healthy adult male participants | Percent of total radioactivity in urine and feces relative to the administered radioactive dose. | Pre-dose to 168 hours post-dose, collection time can be extended | 
| Investigation of the route(s) of elimination and the overall mass balance of IDV184001, following a single oral dose of [14C] IDV184001AN in healthy adult male participants | The percent of the radioactive dose excreted in the urine and feces | Pre-dose to 168 hours post-dose, collection time can be extended | 
| Quantitation of total radioactivity in plasma and whole blood following a single oral dose of [14C] IDV184001AN in healthy adult male participants | AUC[last] (area under the concentration-time curve from time 0 to the time of the last quantifiable concentration calculated using the linear trapezoidal rule) as data permits. | Pre-dose to 168 hours post-dose, collection time can be extended | 
| Quantitation of total radioactivity in plasma and whole blood following a single oral dose of [14C] IDV184001AN in healthy adult male participants | AUC[0-∞] (area under the concentration-time curve from time 0 extrapolated to infinite time) as data permits. | Pre-dose to 168 hours post-dose, collection time can be extended | 
| Quantitation of total radioactivity in plasma and whole blood following a single oral dose of [14C] IDV184001AN in healthy adult male participants | AUC[extrap(%)] (percent of the area under the concentration-time curve due to extrapolation) as data permits. | Pre-dose to 168 hours post-dose, collection time can be extended | 
| Quantitation of total radioactivity in plasma and whole blood following a single oral dose of [14C] IDV184001AN in healthy adult male participants | Cmax (maximum observed concentration) as data permits. | Pre-dose to 168 hours post-dose, collection time can be extended | 
| Quantitation of total radioactivity in plasma and whole blood following a single oral dose of [14C] IDV184001AN in healthy adult male participants | Tmax (time of Cmax) as data permits. | Pre-dose to 168 hours post-dose, collection time can be extended | 
| Quantitation of total radioactivity in plasma and whole blood following a single oral dose of [14C] IDV184001AN in healthy adult male participants | λz (terminal phase rate constant) as data permits. | Pre-dose to 168 hours post-dose, collection time can be extended | 
| Quantitation of total radioactivity in plasma and whole blood following a single oral dose of [14C] IDV184001AN in healthy adult male participants | T1/2 (apparent terminal half-life) as data permits. | Pre-dose to 168 hours post-dose, collection time can be extended | 
| Quantitation of total radioactivity in urine and feces following a single oral dose of [14C] IDV184001AN in healthy adult male participants | Ae[t1-t2] (amount of total radioactivity excreted/recovered within a given collection interval) | Pre-dose to 168 hours post-dose, collection time can be extended | 
| Quantitation of total radioactivity in urine and feces following a single oral dose of [14C] IDV184001AN in healthy adult male participants | CumAe (cumulative amount of total radioactivity excreted/recovered) | Pre-dose to 168 hours post-dose, collection time can be extended | 
| Quantitation of total radioactivity in urine and feces following a single oral dose of [14C] IDV184001AN in healthy adult male participants | %Dose (percent of administered dose excreted/recovered within a given collection interval) | Pre-dose to 168 hours post-dose, collection time can be extended | 
| Quantitation of total radioactivity in urine and feces following a single oral dose of [14C] IDV184001AN in healthy adult male participants | Cum%Dose (cumulative percent of dose excreted/recovered) | Pre-dose to 168 hours post-dose, collection time can be extended | 
| Quantitation of total radioactivity in urine following a single oral dose of [14C] IDV184001AN in healthy adult male participants | CLr (renal clearance) | Pre-dose to 168 hours post-dose, collection time can be extended | 
| Pharmacokinetic profile of unlabelled IDV184001 and M12 in plasma following a single oral dose of [14C] IDV184001AN in healthy adult male participants | AUC[last], as data permits | Pre-dose to 168 hours post-dose | 
| Pharmacokinetic profile of unlabelled IDV184001 and M12 in plasma following a single oral dose of [14C] IDV184001AN in healthy adult male participants | AUC[0-∞], as data permits | Pre-dose to 168 hours post-dose | 
| Pharmacokinetic profile of unlabelled IDV184001 and M12 in plasma following a single oral dose of [14C] IDV184001AN in healthy adult male participants | AUC[extrap(%)], as data permits | Pre-dose to 168 hours post-dose | 
| Pharmacokinetic profile of unlabelled IDV184001 and M12 in plasma following a single oral dose of [14C] IDV184001AN in healthy adult male participants | Cmax, as data permits | Pre-dose to 168 hours post-dose | 
| Pharmacokinetic profile of unlabelled IDV184001 and M12 in plasma following a single oral dose of [14C] IDV184001AN in healthy adult male participants | Tmax, as data permits | Pre-dose to 168 hours post-dose | 
| Pharmacokinetic profile of unlabelled IDV184001 and M12 in plasma following a single oral dose of [14C] IDV184001AN in healthy adult male participants | λz, as data permits | Pre-dose to 168 hours post-dose | 
| Pharmacokinetic profile of unlabelled IDV184001 and M12 in plasma following a single oral dose of [14C] IDV184001AN in healthy adult male participants | T1/2, as data permits | Pre-dose to 168 hours post-dose | 
| Pharmacokinetic profile of unlabelled IDV184001 and M12 in plasma following a single oral dose of [14C] IDV184001AN in healthy adult male participants | Ratio of unlabelled IDV184001 and M12 in plasma to plasma total radioactivity for AUC[last], where appropriate | Pre-dose to 168 hours post-dose | 
| Pharmacokinetic profile of unlabelled IDV184001 and M12 in plasma following a single oral dose of [14C] IDV184001AN in healthy adult male participants | Ratio of unlabelled IDV184001 and M12 in plasma to plasma total radioactivity for Cmax, where appropriate | Pre-dose to 168 hours post-dose | 
| Characterization of metabolite identification, profiling and quantitation for IDV184001 in plasma, urine, and feces following a single oral dose of [14C] IDV184001AN in healthy adult male participants | Determination of % of AUC of each identified metabolites in plasma | Pre-dose to 168 hours post-dose, collection time can be extended | 
| Characterization of metabolite identification, profiling and quantitation for IDV184001 in plasma, urine, and feces following a single oral dose of [14C] IDV184001AN in healthy adult male participants | Determination of % of dose of each identified metabolites in urine | Pre-dose to 168 hours post-dose, collection time can be extended | 
| Characterization of metabolite identification, profiling and quantitation for IDV184001 in plasma, urine, and feces following a single oral dose of [14C] IDV184001AN in healthy adult male participants | Determination of % of dose of each identified metabolites in feces | Pre-dose to 168 hours post-dose, collection time can be extended | 
| Determination of the ratio of total radioactivity concentration equivalents in whole blood versus plasma following a single oral dose of [14C] IDV184001AN in healthy adult male participants | The ratio of total radioactivity concentration equivalents in whole blood relative to plasma at each time-matched determination of total radioactivity in whole blood and plasma | Pre-dose to 168 hours post-dose, collection time can be extended | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assessment of the safety and tolerability (incidence, seriousness, severity, and relatedness of treatment-emergent adverse events) of a single oral dose of [14C] IDV184001AN as determined by adverse event reporting | Incidence, seriousness, severity, and relatedness of treatment-emergent adverse events | From informed consent signature up to 7 weeks (screening to end of study) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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healthy volunteers, ADME, OUD, radiolabel, metabolism