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

Opioid Use Disorder Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05974046
• Other study ID #: INDV-2000-105
• Status: Completed
• Phase: Phase 1
• Start date: July 10, 2023
• Est. completion date: July 21, 2023

Study information

• Verified date: January 2024
• Source: Indivior Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 7
• Est. completion date: July 21, 2023
• Est. primary completion date: July 21, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 19 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Opioid Use Disorder
• Opioid-Related Disorders

Intervention

Drug:
• [14C]IDV184001AN
[14C]-IDV184001AN 200 mg/~100 µCi/ 15 g oral suspension

Locations

Country	Name	City	State
United States	Celerion	Lincoln	Nebraska

Sponsors (1)

Lead Sponsor	Collaborator
Indivior Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	Quantitation of total radioactivity in plasma and whole blood following a single oral dose of [14C] IDV184001AN in healthy adult male participants	AUC[0-8] (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
Primary	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
Primary	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
Primary	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
Primary	Quantitation of total radioactivity in plasma and whole blood following a single oral dose of [14C] IDV184001AN in healthy adult male participants	?z (terminal phase rate constant) as data permits.	Pre-dose to 168 hours post-dose, collection time can be extended
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Pharmacokinetic profile of unlabelled IDV184001 and M12 in plasma following a single oral dose of [14C] IDV184001AN in healthy adult male participants	AUC[0-8], as data permits	Pre-dose to 168 hours post-dose
Primary	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
Primary	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
Primary	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
Primary	Pharmacokinetic profile of unlabelled IDV184001 and M12 in plasma following a single oral dose of [14C] IDV184001AN in healthy adult male participants	?z, as data permits	Pre-dose to 168 hours post-dose
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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)