Clinical trial NCT05974046: Single Dose Study of [14C]-IDV184001AN ([14C]-IDV184001) in Healthy Adult Male Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Opioid Use Disorder
Keywords: healthy volunteers
ADME
OUD
radiolabel
metabolism
Lead sponsor: Indivior Inc.
Sponsor class: INDUSTRY
First posted: 2023-08-03
Enrollment: 7
Sex: MALE
Minimum age (years): 19
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

* Participants are eligible to be included in the study only if all of the following criteria apply:

  1. Participant must be 19 to 55 years of age inclusive, at the time of signing the informed consent.
  2. 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).
  3. Participant must be male and who is healthy as determined by medical evaluation.
  4. 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.
  5. 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.
  6. 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:

  1. 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.
  2. Have clinically significant abnormal biochemistry, haematology or urinalysis results as judged by an Investigator.
  3. Have a history of narcolepsy or sleep apnea.
  4. Have disorders that may interfere with drug absorption, distribution, metabolism and excretion processes.
  5. Current active hepatic or biliary disease.
  6. Participants with cholecystectomy \<90 days prior to the Screening Visit.
  7. Positive test results for HIV-1/HIV-2 antibodies, HBsAg or Hepatitis C antibodies at the Screening Visit.
  8. Have a blood pressure reading outside of the following range: Systolic \<86 or \>149 mmHg; Diastolic \<50 or \>94 mmHg at the Screening Visit.
  9. 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
  10. 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.
  11. 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.
  12. 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.
  13. Any consumption of food or drink containing poppy seeds, grapefruit or Seville oranges within 14 days prior to dosing of study drug.
  14. Regular alcohol consumption \>21 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine).
  15. Positive test result for alcohol and/or drugs of abuse at the Screening Visit or at check-in.
  16. 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.
  17. Blood donation of approximately 500 mL or more within 56 days or plasma donation within 7 days prior to the Screening Visit.
  18. Known hypersensitivity to INDV-2000.
  19. Has less than 1 bowel movement every 2 days.
  20. Recent history of abnormal bowel movements, such as diarrhea, loose stools or constipation, within 2 weeks prior to dosing of study drug.
  21. 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).
  22. 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.
  23. Major surgical procedure (as defined by the Investigator) within 90 days prior to dosing of study drug or still recovering from prior surgery.
  24. Concurrent enrolment in another clinical study, unless it is an observational study.
  25. Participants who are unable, in the opinion of the Investigator, to comply fully with the study requirements.
  26. 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.

Primary outcomes:
measure: Percent of Radioactive Dose Excreted in the Urine, Feces, and Urine+Feces (%Dose) Following a Single Oral Dose of [14C]-IDV184001AN in Healthy Adult Male Participants
timeFrame: Pre-dose to 168 hours post-dose
measure: Cumulative Percent of Radioactive Dose Excreted in the Urine, Feces, and Urine+Feces (Cum%Dose) Following a Single Oral Dose of [14C]-IDV184001AN in Healthy Adult Male Participants
timeFrame: Pre-dose to 168 hours post-dose
measure: Total Radioactivity AUClast in Plasma Following a Single Oral Dose of [14C]-IDV184001AN in Healthy Adult Male Participants
timeFrame: Pre-dose to 168 hours post-dose
measure: Total Radioactivity AUClast in Whole Blood Following a Single Oral Dose of [14C]-IDV184001AN in Healthy Adult Male Participants
timeFrame: Pre-dose to 168 hours post-dose
measure: Total Radioactivity AUC[0-∞] in Plasma Following a Single Oral Dose of [14C]-IDV184001AN in Healthy Adult Male Participants
timeFrame: Pre-dose to 168 hours post-dose
measure: Total Radioactivity AUC[0-∞] in Whole Blood Following a Single Oral Dose of [14C]-IDV184001AN in Healthy Adult Male Participants
timeFrame: Pre-dose to 168 hours post-dose
measure: Total Radioactivity AUC[Extrap(%)] in Plasma Following a Single Oral Dose of [14C]-IDV184001AN in Healthy Adult Male Participants
timeFrame: Pre-dose to 168 hours post-dose
measure: Total Radioactivity AUC[Extrap(%)] in Whole Blood Following a Single Oral Dose of [14C]-IDV184001AN in Healthy Adult Male Participants
timeFrame: Pre-dose to 168 hours post-dose
measure: Total Radioactivity Cmax in Plasma Following a Single Oral Dose of [14C]-IDV184001AN in Healthy Adult Male Participants
timeFrame: Pre-dose to 168 hours post-dose
measure: Total Radioactivity Cmax in Whole Blood Following a Single Oral Dose of [14C]-IDV184001AN in Healthy Adult Male Participants
timeFrame: Pre-dose to 168 hours post-dose
measure: Total Radioactivity Tmax in Plasma and Whole Blood Following a Single Oral Dose of [14C]-IDV184001AN in Healthy Adult Male Participants
timeFrame: Pre-dose to 168 hours post-dose
measure: Total Radioactivity λz in Plasma and Whole Blood Following a Single Oral Dose of [14C]-IDV184001AN in Healthy Adult Male Participants
timeFrame: Pre-dose to 168 hours post-dose
measure: Total Radioactivity Ae[t1-t2] in Urine, Feces, and Urine+Feces Following a Single Oral Dose of [14C]-IDV184001AN in Healthy Adult Male Participants
timeFrame: Pre-dose to 168 hours post-dose
measure: Total Radioactivity T1/2 in Plasma and Whole Blood Following a Single Oral Dose of [14C]-IDV184001AN in Healthy Adult Male Participants
timeFrame: Pre-dose to 168 hours post-dose
measure: Total Radioactivity CumAe in Urine, Feces, and Urine+Feces Following a Single Oral Dose of [14C]-IDV184001AN in Healthy Adult Male Participants
timeFrame: Pre-dose to 168 hours post-dose
measure: Total Radioactivity CLr in Urine Following a Single Oral Dose of [14C]-IDV184001AN in Healthy Adult Male Participants
timeFrame: Pre-dose to 168 hours post-dose
measure: Unlabeled IDV184001 and M12 AUC[Last] in Plasma Following a Single Oral Dose of [14C] IDV184001AN in Healthy Adult Male Participants
timeFrame: Pre-dose to 168 hours post-dose
measure: Unlabeled IDV184001 and M12 AUC[0-∞] in Plasma Following a Single Oral Dose of [14C] IDV184001AN in Healthy Adult Male Participants
timeFrame: Pre-dose to 168 hours post-dose
measure: Unlabeled IDV184001 and M12 AUC[Extrap(%)] in Plasma Following a Single Oral Dose of [14C] IDV184001AN in Healthy Adult Male Participants
timeFrame: Pre-dose to 168 hours post-dose
measure: Unlabeled IDV184001 and M12 Cmax in Plasma Following a Single Oral Dose of [14C] IDV184001AN in Healthy Adult Male Participants
timeFrame: Pre-dose to 168 hours post-dose
measure: Unlabeled IDV184001 and M12 Tmax in Plasma Following a Single Oral Dose of [14C] IDV184001AN in Healthy Adult Male Participants
timeFrame: Pre-dose to 168 hours post-dose
measure: Unlabeled IDV184001 and M12 λz in Plasma Following a Single Oral Dose of [14C] IDV184001AN in Healthy Adult Male Participants
timeFrame: Pre-dose to 168 hours post-dose
measure: Unlabeled IDV184001 and M12 T1/2 in Plasma Following a Single Oral Dose of [14C] IDV184001AN in Healthy Adult Male Participants
timeFrame: Pre-dose to 168 hours post-dose
measure: Ratio of Unlabeled IDV184001 and M12 in Plasma to Plasma Total Radioactivity for AUC[Last] Following a Single Oral Dose of [14C] IDV184001AN in Healthy Adult Male Participants
timeFrame: Pre-dose to 168 hours post-dose
measure: Ratio of Unlabeled IDV184001 and M12 in Plasma to Plasma Total Radioactivity for Cmax Following a Single Oral Dose of [14C] IDV184001AN in Healthy Adult Male Participants
timeFrame: Pre-dose to 168 hours post-dose
measure: Percentage of Total AUC of Each Identified Metabolite in Plasma Following a Single Oral Dose of [14C] IDV184001AN in Healthy Adult Male Participants
timeFrame: Pre-dose to 168 hours post-dose
measure: Percentage of Dose of Each Identified Metabolite in Urine Following a Single Oral Dose of [14C] IDV184001AN in Healthy Adult Male Participants
timeFrame: Pre-dose to 168 hours post-dose
measure: Percentage of Total AUC of Each Identified Metabolite in Feces Following a Single Oral Dose of [14C] IDV184001AN in Healthy Adult Male Participants
timeFrame: Pre-dose to 168 hours post-dose
measure: 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
timeFrame: Pre-dose to 168 hours post-dose
Secondary outcomes:
measure: 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
timeFrame: From informed consent signature to end of study (up to 11 days)
Other outcomes:
Locations:
city: Lincoln
country: United States
facility: Celerion
state: Nebraska
Study officials:
affiliation: Indivior Inc.
name: Global Director Clinical Development
role: STUDY_DIRECTOR
References: