Clinical trial NCT04413552: INDV-2000 First in Human
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Opioid Dependence
Lead sponsor: Indivior Inc.
Sponsor class: INDUSTRY
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2020-06-04
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Part I - sequential escalating dose cohorts; within each dose cohort participants will be randomized to INDV-2000 or matching placebo in a 3:1 ratio.

Part II - single cohort crossover study in which participants will receive INDV-2000 on 2 occasions separated by a 1-week washout period, once under fasting conditions and once after a standard high-fat breakfast.
Primary purpose: TREATMENT

Brief summary: This study is a single ascending dose (SAD) study conducted to identify the maximum tolerated dose (MTD) of INDV-2000. 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.


Eligibility criteria: Inclusion Criteria:

* Must be able to verbalize understanding the consent form, able to provide written informed consent, and verbalize willingness to complete study procedures, and be able to comply with protocol requirements, rules and regulations of the 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 and willing to consume a high-fat meal.
* Body mass index (BMI) within 18.0 to 30.0 kg/m\^2, 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 human immunodeficiency virus (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.

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
timeFrame: From first dose of study drug to end of study participation for each cohort; 11 days in Part 1 and 7 days in Part II, Period 1 (fasted conditions) and 10 days in Part II, Period 2 (fed conditions).
Secondary outcomes:
measure: Number of Participants With Clinically Significant Laboratory Findings
timeFrame: From first dose of study drug to end of study participation for each cohort; 11 days in Part I and 7 days in Part II, Period 1 (fasted conditions) and 10 days in Part II, Period 2 (fed conditions).
measure: Number of Participants With Clinically Significant Changes in Vital Signs
timeFrame: From first dose of study drug to end of study participation for each cohort; 11 days in Part 1 and 7 days in Part II, Period 1 (fasted conditions) and 10 days in Part II, Period 2 (fed conditions).
measure: Number of Participants With Clinically Significant Electrocardiogram (ECG) Findings
timeFrame: From first dose of study drug to end of study participation for each cohort; 11 days in Part I and 7 days in Part II, Period 1 (fasted conditions) and 10 days in Part II, Period 2 (fed conditions).
measure: Number of Participants With Clinically Significant Physical Examination Findings
timeFrame: From first dose of study drug to end of study participation for each cohort; 11 days in Part I and 7 days in Part II, Period 1 (fasted conditions) and 10 days in Part II, Period 2 (fed conditions).
measure: Part I: Maximum Observed Plasma Concentration (Cmax) of INDV-2000 After a Single Dose
timeFrame: Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Part I: Time to Maximum Observed Plasma Concentration (Tmax) of INDV-2000 After a Single Dose
timeFrame: Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Part I: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC0-last) of INDV-2000 After A Single Dose
timeFrame: Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Part I: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of INDV-2000 After A Single Dose
timeFrame: Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Part I: Apparent Plasma Clearance (CL/F) of INDV-2000 After a Single Dose
timeFrame: Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Part I: Plasma Terminal Half-life of INDV-2000 After a Single Dose
timeFrame: Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Part I: Maximum Observed Plasma Concentration (Cmax) of M12 After a Single Dose of INDV-2000
timeFrame: Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Part I: Time to Maximum Observed Plasma Concentration (Tmax) of M12 After a Single Dose of INDV-2000
timeFrame: Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Part I: Area Under the Plasma Concentration-time Curve From Time Zero to the Time of Last Quantifiable Concentration of M12 After A Single Dose of INDV-2000
timeFrame: Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Part I: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M12 After A Single Dose of INDV-2000
timeFrame: Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Part I: Plasma Terminal Half-life of M12 After a Single Dose of INDV-2000
timeFrame: Day 1 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Part II: Cmax of INDV-2000 After a Single Dose Under Fasting and Fed Conditions
timeFrame: Day 1 and Day 8 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Part II: Tmax of INDV-2000 After a Single Dose Under Fasting and Fed Conditions
timeFrame: Day 1 and Day 8 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Part II: AUC0-last of INDV-2000 After a Single Dose Under Fasting and Fed Conditions
timeFrame: Day 1 and Day 8 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Part II: AUC0-inf of INDV-2000 After a Single Dose Under Fasting and Fed Conditions
timeFrame: Day 1 and Day 8 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Part II: Apparent Clearance of INDV-2000 After a Single Dose Under Fasting and Fed Conditions
timeFrame: Day 1 and Day 8 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Part II: Plasma Terminal Half-life of INDV-2000 After a Single Dose Under Fasting and Fed Conditions
timeFrame: Day 1 and Day 8 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Part II: Cmax of M12 After a Single Dose of INDV-2000 Under Fasting and Fed Conditions
timeFrame: Day 1 and Day 8 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Part II: Tmax of M12 After a Single Dose of INDV-2000 Under Fasting and Fed Conditions
timeFrame: Day 1 and Day 8 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Part II: AUC0-last of M12 After a Single Dose of INDV-2000 Under Fasting and Fed Conditions
timeFrame: Day 1 and Day 8 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Part II: AUC0-inf of M12 After a Single Dose of INDV-2000 Under Fasting and Fed Conditions
timeFrame: Day 1 and Day 8 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
measure: Part II: Plasma Terminal Half-life of M12 After a Single Dose of INDV-2000 Under Fasting and Fed Conditions
timeFrame: Day 1 and Day 8 pre-dose and at 0.5, 1, 2, 3, 4, 6, 8, 12, 24, 48, and 72 hours post-dose
Other outcomes:
Locations:
city: Overland Park
country: United States
facility: Altasciences Clinical Kansas
state: Kansas
Study officials:
affiliation: Altasciences Company Inc.
name: Martin Kankam
role: PRINCIPAL_INVESTIGATOR
References: