Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AJM347 in Healthy Male Caucasian and Japanese Subjects in the Fasted and Fed State

A First-in-Human, Randomised, Double Blind, Placebo Controlled, Single and Multiple Ascending Oral Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AJM347 in Healthy Male Caucasian and Japanese Subjects in the Fasted and Fed State

This study will be conducted to determine the safety and tolerability of single and multiple oral ascending doses of AJM347 in healthy male participants, and to assess the pharmacodynamic response following single and multiple oral ascending doses of AJM347 in the same population. This study will also aim to determine the single and multiple oral ascending dose pharmacokinetics of AJM347 and its metabolite in healthy male participants, and to determine the effect of food on the single and multiple oral dose pharmacokinetics of AJM347 and its metabolite in the same population.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: Placebo; Drug: AJM347

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Leeds, United Kingdom
    • Covance Clinical Research Unit (CRU) Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

Main Inclusion Criteria for all participants:

• Participants will be male
• Participants will be in good health

Main Inclusion Criteria for Japanese participants:

• Be ≥20 to ≤45 years of age
• Have body mass index (BMI) ≥18.5 to ≤25.0 kilograms per meters squared (kg/m^2)
• Be Japanese

Main Inclusion Criteria for Caucasian participants:

• Be ≥18 to ≤45 years of age
• Have a BMI ≥18.5 to ≤30.0 kg/m^2
• Be Caucasian

Exclusion Criteria:

Main Exclusion Criteria for all participants:

Participants will be excluded from the study if they satisfy any of the following criteria at the Screening visit, unless otherwise stated.

• Participants who have donated or lost ≥200 milliliters (mL) blood within 1 month or ≥400 mL within 3 months prior to Check-in
• Participants who have an abnormality in heart rate, blood pressure, temperature, or respiration rate at Screening

• Participants who have:

  • a positive urine drugs of abuse screen;
  • a positive alcohol breath test
• Participants who have an abnormality in the 12-lead electrocardiogram (ECG) at Screening
• Participants who are still participating in another clinical study (eg, attending follow-up visits) or who have participated in a clinical study involving administration of an investigational drug (new chemical entity) in the past 3 months prior to first dose administration
• Participants who have a significant history of drug allergy, as determined by the Investigator
• Participants who have any clinically significant abnormal physical examination finding

• Participants who:

  • are carriers of the hepatitis B surface antigen (HBsAg);
  • are carriers of the hepatitis C antibody;
  • have a positive result for the test for human immunodeficiency virus (HIV) antibodies
• Participants who, in the opinion of the Investigator, should not participate in this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Part 1: AJM347; Caucasian and Japanese participants will be randomized to receive one of eight and four single oral doses of AJM347, respectively, administered in the fasted state on Day 1.	Drug: AJM347; Oral administration
PLACEBO_COMPARATOR: Part 1: Placebo; Caucasian and Japanese participants will be randomized to receive one of eight and four single oral doses of matching placebo, respectively, administered in the fasted state on Day 1.	Drug: Placebo; Oral administration
EXPERIMENTAL: Part 2: Low-dose AJM347; Caucasian and Japanese participants will receive a "low" dose of AJM347 (at different frequencies and in either a fed or fasted state) on Day 1 of each of 6 sequential treatment periods.	Drug: AJM347; Oral administration
EXPERIMENTAL: Part 2: High-dose AJM347; Caucasian and Japanese participants will receive a "high" dose of AJM347 (at different frequencies and in either a fed or fasted state) on Day 1 of each of 2 sequential treatment periods (the frequency and timing with respect to meals will be determined after review of the data from the low-dose AJM347 groups).	Drug: AJM347; Oral administration
EXPERIMENTAL: Part 3: AJM347; Caucasian and Japanese participants will be randomized to receive one of three single doses of AJM347 on the morning of Day 1 and multiple daily doses beginning on the morning of Day 3, with the last dose received on the evening of Day 9. The actual doses, dosing frequencies, and timings with respect to meals to be employed in Part 3 of the study will be determined after review of the data from dose groups in Parts 1 and 2 of the study.	Drug: AJM347; Oral administration
PLACEBO_COMPARATOR: Part 3: Placebo; Caucasian and Japanese participants will be randomized to receive one of three single doses of matching placebo on the morning of Day 1 and multiple daily doses beginning on the morning of Day 3, with the last dose received on the evening of Day 9. The actual doses, dosing frequencies, and timings with respect to meals to be employed in Part 3 of the study will be determined after review of the data from dose groups in Parts 1 and 2 of the study.	Drug: Placebo; Oral administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with any adverse event (AE)	An AE is any untoward medical occurrence in a patient or clinical investigation participant administered an investigational product. An AE does not necessarily have a causal relationship with the medicinal product.	Part 1, up to Days 7 to 9; Part 2, up to Days 7 to 9; Part 3, up to Day 15 (Parts 1, 2, and 3 are not continuous)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with abnormal, clinically significant physical examination findings	Clinical significance will be determined by the investigator.	Part 1, up to Days 7 to 9; Part 2, up to Days 7 to 9; Part 3, up to Day 15 (Parts 1, 2, and 3 are not continuous)
Number of participants with abnormal, clinically significant vital sign values	Clinical significance will be determined by the investigator.	Part 1, up to Days 7 to 9; Part 2, up to Days 7 to 9; Part 3, up to Day 15 (Parts 1, 2, and 3 are not continuous)
Number of participants with abnormal, clinically significant 12-lead electrocardiogram (ECG) values	Clinical significance will be determined by the investigator.	Part 1, up to Days 7 to 9; Part 2, up to Days 7 to 9; Part 3, up to Day 15 (Parts 1, 2, and 3 are not continuous)
Number of participants with abnormal, clinically significant clinical laboratory values	Clinical significance will be determined by the investigator.	Part 1, up to Days 7 to 9; Part 2, up to Days 7 to 9; Part 3, up to Day 15 (Parts 1, 2, and 3 are not continuous)
Mean plasma concentrations of AJM347 and its metabolite	Blood samples will be collected at the specified time points for the determination of plasma concentrations of AJM347 and its metabolite.	Part 1, Days 1 to 3; Part 2, Days 1 to 3; Part 3, Days 1 to 3, Day 7, Days 9 to 11 (Parts 1, 2, and 3 are not continuous)
Mean urinary concentrations of AJM347 and its metabolite	Urine samples will be collected at the specified time points for the determination of urine concentrations of AJM347 and its metabolite.	Part 1, Days 1 to 3; Part 3, Days 1 to 10
Inhibition rate of ligand-binding activity	The rate of inhibition of ligand-protein binding will be measured.	Part 1, Days 1 and 2; Part 3, Days 1 and 2, Days 7, 9, and 10

Collaborators and Investigators

• Sponsor: EA Pharma Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 25, 2017
• Primary Completion (ACTUAL): July 6, 2018
• Study Completion (ACTUAL): July 6, 2018

Study Registration Dates

• First Submitted: April 25, 2017
• First Submitted That Met QC Criteria: April 25, 2017
• First Posted (ACTUAL): April 28, 2017

Study Record Updates

• Last Update Posted (ACTUAL): August 29, 2018
• Last Update Submitted That Met QC Criteria: August 28, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: pharmacokinetics; pharmacodynamics; AJM347; food effect study
• Other Study ID Numbers: AJM347/CP1; 2017-000259-17 (EUDRACT_NUMBER); 1009306/8349634 (OTHER: Covance Clinical Research Unit)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No