Oral Bioavailability,and Food Effect Study and Single Ascending Dose PK Study in Healthy Male Volunteers

A Phase 1, Randomized Trial to Compare the Oral Bioavailability of Indoximod Salt and Base Formulations and the Effect of Food (Part 1) and to Evaluate the PK and Safety of Single Ascending Doses of Indoximod (Part 2) in Healthy Male Volunteers

This 2-part study will assess the effect of formulation and food on the pharmacokinetics of Indoximod in healthy volunteers. Part 1 is an open-label, 3-period, 6-sequence study. Participants will receive single doses of Indoximod base or salt formulation, in the fasted or fed state. Part 2 is a randomized single ascending dose study of indoximod salt formulation to characterize the PK profile and determine the safety and tolerability of each dose in healthy male volunteers.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Other: Placebo; Drug: Indoximod base formulation; Drug: Indoximod HCL (salt) formulation

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • INC Research/InVentiv Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male subjects 18 to 55 years of age, inclusive.
• Body mass index (BMI) of 18.0 to 30.0 kg/m2, and a minimum weight of 50.0 kg.
• Non-smoker for at least 3 months prior to Screening.
• Male subjects with female sexual partners of childbearing potential must be using and willing to continue using medically acceptable contraception
• Signed and dated written informed consent

Exclusion Criteria:

• History or presence of any clinically significant abnormality, illness, or disease which, in the opinion of the investigator, may either put the subject at risk because of participation in the study or influence the validity of the results of the study.
• Subjects with autoimmune conditions, inflammatory bowel disease, rheumatoid arthritis, and/or subjects who have undergone an organ transplant.
• Self-reported history of substance or alcohol dependence within the past 2 years, and/or has ever participated or plans to participate in a substance or alcohol rehabilitation program to treat their substance or alcohol dependence.
• Any medical/surgical procedure or trauma within 4 weeks of the first study drug administration or planned within 1 month of study completion.
• Positive urine drug screen.
• Positive breath alcohol test.
• Evidence of clinically significant hepatic or renal impairment
• Inability to fast for a minimum of 14 hours.
• Inability to swallow large capsules/tablets.
• Positive for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
• Donation or loss of more than 500 mL whole blood within 1 month preceding entry into the Treatment phase and throughout the study.
• Difficulty with venous access or unsuitable or unwilling to undergo catheter insertion.
• History of severe allergic reaction (including anaphylaxis) to any substance, or previous status asthmaticus.
• Treatment with an investigational drug within 5 times the elimination half-life, if known (eg, a marketed product), or within 30 days (if the elimination half-life is unknown) prior to first drug administration or is concurrently enrolled in any research judged not to be scientifically or medically compatible with this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Bioavailability and Food Effect; Subjects will be randomized to receive the following 3 regimens in randomized sequence: Single dose of Indoximod base formulation under fasting conditions; Single dose of Indoximod HCL (salt) formulation under fed conditions; Single dose of Indoximod HCL (salt) formulation under fasting conditions	Other: Placebo; Specified dose on specified days; Drug: Indoximod base formulation; Specified dose on specified days; Drug: Indoximod HCL (salt) formulation; Specified dose on specified days
Experimental: Part 2: Single Ascending Dose	Other: Placebo; Specified dose on specified days; Drug: Indoximod HCL (salt) formulation; Specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Plasma Concentration-Time Curve	Part 1 (Food Effect)	up to 20 Days
Pharmacokinetics: Serum concentrations (Cmax/Steady State)	Part 1 (Food Effect)	up to 20 Days
Pharmacokinetics: Serum concentrations (Cmax/Steady State)	Part 2 (Single rising dose)	up to 4 Days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with adverse events	Part 1	up to 34 Days
Percentage of patients with adverse events	Single rising dose	up to 16 Days

Collaborators and Investigators

• Sponsor: NewLink Genetics Corporation
• Investigators: Study Director: Eugene Kennedy, MD, NewLink Genetics Inc

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2017
• Primary Completion (Actual): January 25, 2018
• Study Completion (Actual): April 16, 2018

Study Registration Dates

• First Submitted: December 10, 2017
• First Submitted That Met QC Criteria: December 10, 2017
• First Posted (Actual): December 13, 2017

Study Record Updates

• Last Update Posted (Actual): May 28, 2020
• Last Update Submitted That Met QC Criteria: May 26, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Indoximod
• Additional Relevant MeSH Terms: Psychotropic Drugs; Antidepressive Agents; Antidepressive Agents, Second-Generation; Tryptophan
• Other Study ID Numbers: NLG2108

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes