INDV-2000 First in Human

• ClinicalTrials.gov Identifier: NCT04413552
• Recruitment Status: Recruiting
• First Posted: June 4, 2020
• Last Update Posted: February 15, 2021
• Sponsor: Indivior Inc.
• Collaborator: National Institute on Drug Abuse (NIDA)
• Information provided by (Responsible Party): Indivior Inc.

Study Description

Brief Summary:

This study will be a single ascending dose (SAD) study conducted to identify the maximum tolerated dose (MTD). After completion of the SAD portion of the study and acceptable safety evaluation, a food-interaction, single-dose study under fed and fasted conditions will be conducted.

Condition or disease	Intervention/treatment	Phase
Opioid Dependence	Drug: INDV-2000; Other: matching placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 56 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: Part I-sequential escalating doses will be administered Part II-study medication will be administered under fed and fasted conditions
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase I, Double-blind, Placebo-controlled, Randomized, Single Ascending Dose Study to Assess the Safety, Tolerability and Pharmacokinetics of INDV-2000 (C4X_3256) Under Fasting and Fed Conditions in Healthy Volunteers
• Actual Study Start Date: July 6, 2020
• Estimated Primary Completion Date: May 6, 2021
• Estimated Study Completion Date: May 6, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: Part I-Active arm; Each cohort will be randomized to either placebo-matched or active INDV-2000 in increasing doses. In each cohort a sentinel group of 2 subjects will be randomized and dosed ahead of the rest of the cohort. A review of safety data will be completed prior to administration of doses to the remainder of the cohort	Drug: INDV-2000; Study medication (active) will be administered as either powder in solution or powder in capsule, depending on dose administered.; Other Name: C4X
Placebo Comparator: Part II-Placebo arm; Each cohort will be randomized to either placebo-matched or active INDV-2000 in increasing doses. In each cohort a sentinel group of 2 subjects will be randomized and dosed ahead of the rest of the cohort. A review of safety data will be completed prior to administration of doses to the remainder of the cohort	Other: matching placebo; Study medication (placebo) will be administered as either powder in solution or powder in capsule, depending on dose administered.; Other Name: placebo
Experimental: Part II-Active arm-fed; Study medication will be administered after a high fat meal. Dose to be determine based on a well-tolerated dose studied in Part I.	Drug: INDV-2000; Study medication (active) will be administered as either powder in solution or powder in capsule, depending on dose administered.; Other Name: C4X
Experimental: Part II-Active arm-fasting; Study medication will be administered under fasted conditions. Dose to be determine based on a well-tolerated dose studied in Part I.	Drug: INDV-2000; Study medication (active) will be administered as either powder in solution or powder in capsule, depending on dose administered.; Other Name: C4X

Outcome Measures

Primary Outcome Measures :

1. Safety of single doses of INDV-2000 as determined by adverse event reporting [ Time Frame: Adverse events will be measured from time of informed consent to end of study participation for each cohort (up to 45 days) ]
   Occurrence of any adverse event

Secondary Outcome Measures :

1. Incidence of treatment emergent adverse events (TEAEs) as measured by clinically significant changes in laboratory values [ Time Frame: Labs will be assessed from screening until the end of subject participation (end of study or early termination visit as applicable), up to 45 days from the screening visit. ]
   Observed values and changes from baseline in clinical laboratory parameters will be summarized by analysis visit (frequency and percentages for each category). Clinically significant changes from baseline requiring additional assessment or treatment will be reported as adverse events.
2. Incidence of TEAEs as measured by changes in electrocardiogram (ECG) intervals [ Time Frame: Electrocardiographic assessments will be performed at screening, and intermittently until the end of subject participation (end of study or early termination visit as applicable), up to 45 days from the screening visit ]
   Observed values and changes from baseline in ECG interval measurements will be summarized by analysis visit. Clinically significant changes from baseline will be reported as adverse events
3. Incidence of TEAEs as measured by changes from baseline in vital signs measures [ Time Frame: Vital signs will be assessed from screening, until the end of subject participation (end of study or early termination visit as applicable), up to 45 days from the screening visit. ]
   Observed values and changes from baseline in vital signs (blood pressure, respiratory rate, heart rate and temperature) will be summarized by analysis visit. Clinically significant changes will be reported as adverse events.
4. Incidence of TEAEs as measured by physical examination changes [ Time Frame: Labs will be assessed from screening, until the end of subject participation (end of study or early termination visit as applicable) ]
   Clinically significant changes in physical examination findings will be reported as adverse events
5. Plasma pharmacokinetic (PK) parameters of single doses of INDV-2000 as measured by maximum concentration (Cmax) [ Time Frame: PK samples will be obtained at selected timepoints from pre-dose until 72 hours post-dose ]
   Concentrations for INDV-2000 and its metabolite (M12) will be measured
6. Plasma PK parameters of single doses of INDV-2000 as measured by time to reach maximum plasma concentration (Tmax) [ Time Frame: PK samples will be obtained at selected timepoints from pre-dose until 72 hours post-dose ]
   Concentrations for INDV-2000 and its metabolite (M12) will be measured
7. Plasma PK parameters of single doses of INDV-2000 as measured by area under the plasma concentration-time curve (AUC) [ Time Frame: PK samples will be obtained at selected timepoints from pre-dose until 72 hours post-dose ]
   Concentrations for INDV-2000 and its metabolite (M12) will be measured
8. Plasma PK parameters of single doses of INDV-2000 as measured by plasma clearance [ Time Frame: PK samples will be obtained at selected timepoints from pre-dose until 72 hours post-dose ]
   Concentrations for INDV-2000 and its metabolite (M12) will be measured
9. Plasma PK parameters of single doses of INDV-2000 as measured by plasma terminal half-life [ Time Frame: PK samples will be obtained at selected timepoints from pre-dose until 72 hours post-dose ]
   Concentrations for INDV-2000 and its metabolite (M12) will be measured

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Must be able to verbalize understanding of the consent form, able to provide written informed consent, and verbalize willingness to complete study procedures, be able to comply with protocol requirements, rules and regulations of study site, and be likely to complete all the study interventions.
• Must be considered a healthy male or non-childbearing female for Part I
• For part II, must be a healthy male who did not participate in Part I who is willing to consume a high-fat meal.
• Body mass index (BMI) within 18.0 to 30.0 kg/m2, inclusive (minimum weight of at least 50.0 kg at Screening)
• Male subjects who are sexually active with female partners of child-bearing potential must use, with their partner, a condom plus an approved method of effective contraception from time of screening until 90 days after last dose of Investigational Medicinal Product (IMP). Additionally, male subjects must agree to not donate sperm during the study and for at least 90 days from last dose of IMP.

Exclusion Criteria:

• Have a medical history of clinically significant neurological, cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease, or psychiatric disorder as judged by an Investigator,
• Have clinically significant abnormal biochemistry, hematology or urinalysis results as judged by an Investigator,
• Have a history of narcolepsy or other significant sleep disorders
• Have disorders that may interfere with drug absorption, distribution, metabolism and excretion (ADME) processes,
• Positive test results for HIV-1/HIV-2 Antibodies, Hepatitis B surface Antigen (HBsAg) or Hepatitis C Antibody (HCVAb).
• Serious cardiac illness or other medical condition including, but not limited to: Uncontrolled arrhythmias; History of congestive heart failure (CHF); Myocardial infarction <6 months from receipt of first dose of IMP; Uncontrolled symptomatic angina; Corrected QT value (QTcF) >450 msec for males and >470 msec for females or history of prolonged QT syndrome; Have a blood pressure reading outside of the following range: Systolic <86 or >149 mmHg; Diastolic <50 or >94 mmHg
• Current active hepatic or biliary disease. Subjects with Cholecystectomy <90 days prior to screening.
• Regular alcohol consumption in males >21 units per week and females >14 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 screening or prior to the first IMP administration.
• Current smokers and those who have smoked within the last 90 days. Current users of e-cigarettes and nicotine replacement products, and those who have used these products within the last 90 days.
• Concurrent treatment or treatment with an investigational drug within 30 days prior to the first dose.
• Blood donation of approximately 500 mL within 56 days or plasma donation within 7 days of screening.
• Subjects who are taking, or have taken, any prescribed or over-the-counter drugs (other than 2 g per day acetaminophen, hormone replacement therapy, hormonal contraception) or herbal remedies in the 14 days before IMP administration. Exceptions may apply on a case by case basis if considered not to interfere with the objectives of the study, as agreed by an Investigator and Sponsor's Medical Monitor.
• Any consumption of food or drink containing poppy seeds, grapefruit or Seville oranges within 7 days prior to the IMP administration
• Treatment with any known drugs that are moderate or strong inhibitors/inducers of cytochrome P450 (CYP) 3A4 within 30 days prior to first dose of IMP.
• Known allergy or hypersensitivity to IMP or its excipients.
• Any condition that, in the opinion of an Investigator, would interfere with evaluation of the IMP or interpretation of subject safety or study results.
• Affiliated with, or a family member of, site staff directly involved in the study, or anyone with a financial interest in the outcome of the study.
• Subjects who are unable, in the opinion of an Investigator, to comply fully with the study requirements.

Contacts and Locations

Contacts

Contact: Robert Dobbins; 804 379-1090; robert.dobbins@indivior.com

Contact: Sunita Shinde; 804 379-1090; sunita.shinde@indivior.com

Locations

United States, Kansas

Altasciences Clinical Kansas; Recruiting

Overland Park, Kansas, United States, 66212

Contact: Samantha Reiber sreiber@altasciences.com

Sponsors and Collaborators

Indivior Inc.

National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Martin Kankam; altasciences

More Information

• Responsible Party: Indivior Inc.
• ClinicalTrials.gov Identifier: NCT04413552
• Other Study ID Numbers: INDV-2000-101
• First Posted: June 4, 2020
• Last Update Posted: February 15, 2021
• Last Verified: February 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Opioid-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders