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
Overview
- Phase
- Phase 1
- Intervention
- [14C]IDV184001AN
- Conditions
- Opioid Use Disorder
- Sponsor
- Indivior Inc.
- Enrollment
- 7
- Locations
- 1
- Primary Endpoint
- 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
- Status
- Completed
- Last Updated
- last year
Overview
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.
Investigators
Eligibility Criteria
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:
Arms & Interventions
Treatment
\[14C\]IDV184001AN
Intervention: [14C]IDV184001AN
Outcomes
Primary Outcomes
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
Time Frame: Pre-dose to 168 hours post-dose
Percentage of total radioactivity recovered relative to dose (%Dose) in urine, feces and urine + feces (by time interval)
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
Time Frame: Pre-dose to 168 hours post-dose
Percentage of cumulative total radioactivity recovered relative to dose (Cum%Dose) in urine, feces, and urine+feces (0-168 hours)
Total Radioactivity AUClast in Plasma Following a Single Oral Dose of [14C]-IDV184001AN in Healthy Adult Male Participants
Time Frame: Pre-dose to 168 hours post-dose
Total radioactivity pharmacokinetic parameter: 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 permit.
Total Radioactivity AUClast in Whole Blood Following a Single Oral Dose of [14C]-IDV184001AN in Healthy Adult Male Participants
Time Frame: Pre-dose to 168 hours post-dose
Total radioactivity pharmacokinetic parameter: 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 permit.
Total Radioactivity AUC[0-∞] in Plasma Following a Single Oral Dose of [14C]-IDV184001AN in Healthy Adult Male Participants
Time Frame: Pre-dose to 168 hours post-dose
Total radioactivity pharmacokinetic parameter: AUC\[0-∞\] (area under the concentration-time curve from time 0 extrapolated to infinite time) as data permit.
Total Radioactivity AUC[0-∞] in Whole Blood Following a Single Oral Dose of [14C]-IDV184001AN in Healthy Adult Male Participants
Time Frame: Pre-dose to 168 hours post-dose
Total radioactivity pharmacokinetic parameter: AUC\[0-∞\] (area under the concentration-time curve from time 0 extrapolated to infinite time) as data permit.
Total Radioactivity AUC[Extrap(%)] in Plasma Following a Single Oral Dose of [14C]-IDV184001AN in Healthy Adult Male Participants
Time Frame: Pre-dose to 168 hours post-dose
Total radioactivity pharmacokinetic parameter: AUC\[extrap(%)\] (percent of the area under the concentration-time curve due to extrapolation) as data permit.
Total Radioactivity AUC[Extrap(%)] in Whole Blood Following a Single Oral Dose of [14C]-IDV184001AN in Healthy Adult Male Participants
Time Frame: Pre-dose to 168 hours post-dose
Total radioactivity pharmacokinetic parameter: AUC\[extrap(%)\] (percent of the area under the concentration-time curve due to extrapolation) as data permit.
Total Radioactivity Cmax in Plasma Following a Single Oral Dose of [14C]-IDV184001AN in Healthy Adult Male Participants
Time Frame: Pre-dose to 168 hours post-dose
Total radioactivity pharmacokinetic parameter: Cmax (maximum observed concentration) as data permit. The Units of Measure for Cmax (i.e., " ngEq/mL") reflect the peak concentration that occurred from pre-dose to 168 hours post-dose.
Total Radioactivity Cmax in Whole Blood Following a Single Oral Dose of [14C]-IDV184001AN in Healthy Adult Male Participants
Time Frame: Pre-dose to 168 hours post-dose
Total radioactivity pharmacokinetic parameter: Cmax (maximum observed concentration) as data permit. The Units of Measure for Cmax (i.e., " ngEq/g)") reflect the peak concentration that occurred from pre-dose to 168 hours post-dose.
Total Radioactivity Tmax in Plasma and Whole Blood Following a Single Oral Dose of [14C]-IDV184001AN in Healthy Adult Male Participants
Time Frame: Pre-dose to 168 hours post-dose
Total radioactivity pharmacokinetic parameter: Tmax (time of Cmax) as data permit.
Total Radioactivity λz in Plasma and Whole Blood Following a Single Oral Dose of [14C]-IDV184001AN in Healthy Adult Male Participants
Time Frame: Pre-dose to 168 hours post-dose
Total radioactivity pharmacokinetic parameter: λz (terminal phase rate constant) as data permit.
Total Radioactivity Ae[t1-t2] in Urine, Feces, and Urine+Feces Following a Single Oral Dose of [14C]-IDV184001AN in Healthy Adult Male Participants
Time Frame: Pre-dose to 168 hours post-dose
Ae\[t1-t2\] (amount of total radioactivity excreted/recovered in urine, feces, and urine+feces within a given collection interval)
Total Radioactivity T1/2 in Plasma and Whole Blood Following a Single Oral Dose of [14C]-IDV184001AN in Healthy Adult Male Participants
Time Frame: Pre-dose to 168 hours post-dose
Total radioactivity pharmacokinetic parameter: T1/2 (apparent terminal half-life) as data permit.
Total Radioactivity CumAe in Urine, Feces, and Urine+Feces Following a Single Oral Dose of [14C]-IDV184001AN in Healthy Adult Male Participants
Time Frame: Pre-dose to 168 hours post-dose
CumAe (cumulative amount of total radioactivity excreted/recovered in urine, feces, and urine+feces) (0-168 hour)
Total Radioactivity CLr in Urine Following a Single Oral Dose of [14C]-IDV184001AN in Healthy Adult Male Participants
Time Frame: Pre-dose to 168 hours post-dose
CLr (renal clearance)
Unlabeled IDV184001 and M12 AUC[Last] in Plasma Following a Single Oral Dose of [14C] IDV184001AN in Healthy Adult Male Participants
Time Frame: Pre-dose to 168 hours post-dose
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 permit.
Unlabeled IDV184001 and M12 AUC[0-∞] in Plasma Following a Single Oral Dose of [14C] IDV184001AN in Healthy Adult Male Participants
Time Frame: Pre-dose to 168 hours post-dose
AUC\[0-∞\] (area under the concentration-time curve from time 0 extrapolated to infinite time) as data permit.
Unlabeled IDV184001 and M12 AUC[Extrap(%)] in Plasma Following a Single Oral Dose of [14C] IDV184001AN in Healthy Adult Male Participants
Time Frame: Pre-dose to 168 hours post-dose
AUC\[extrap(%)\] (percent of the area under the concentration-time curve due to extrapolation) as data permit.
Unlabeled IDV184001 and M12 Cmax in Plasma Following a Single Oral Dose of [14C] IDV184001AN in Healthy Adult Male Participants
Time Frame: Pre-dose to 168 hours post-dose
Cmax (maximum observed concentration) as data permit.
Unlabeled IDV184001 and M12 Tmax in Plasma Following a Single Oral Dose of [14C] IDV184001AN in Healthy Adult Male Participants
Time Frame: Pre-dose to 168 hours post-dose
Tmax (time of Cmax) as data permit.
Unlabeled IDV184001 and M12 λz in Plasma Following a Single Oral Dose of [14C] IDV184001AN in Healthy Adult Male Participants
Time Frame: Pre-dose to 168 hours post-dose
λz (terminal phase rate constant) as data permit.
Unlabeled IDV184001 and M12 T1/2 in Plasma Following a Single Oral Dose of [14C] IDV184001AN in Healthy Adult Male Participants
Time Frame: Pre-dose to 168 hours post-dose
T1/2 (apparent terminal half-life) as data permit.
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
Time Frame: Pre-dose to 168 hours post-dose
Ratio of unlabeled IDV184001 and M12 in plasma to plasma total radioactivity for 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), where appropriate
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
Time Frame: Pre-dose to 168 hours post-dose
Ratio of unlabeled IDV184001 and M12 in plasma to plasma total radioactivity for Cmax (maximum observed concentration), where appropriate
Percentage of Total AUC of Each Identified Metabolite in Plasma Following a Single Oral Dose of [14C] IDV184001AN in Healthy Adult Male Participants
Time Frame: Pre-dose to 168 hours post-dose
Determination of percentage of AUC (area under the concentration-time curve) of each identified metabolites to total AUC in plasma
Percentage of Dose of Each Identified Metabolite in Urine Following a Single Oral Dose of [14C] IDV184001AN in Healthy Adult Male Participants
Time Frame: Pre-dose to 168 hours post-dose
Determination of percentage of dose of each identified metabolites in urine
Percentage of Total AUC of Each Identified Metabolite in Feces Following a Single Oral Dose of [14C] IDV184001AN in Healthy Adult Male Participants
Time Frame: Pre-dose to 168 hours post-dose
Determination of percentage of AUC (area under the concentration-time curve) of M436 metabolite to total AUC in feces
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
Time Frame: Pre-dose to 168 hours post-dose
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
Secondary Outcomes
- 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(From informed consent signature to end of study (up to 11 days))