HMPL004-6599 Phase I Dose-escalating Study

NCT03597971 | Terminated Phase 1 DMC

• 1 other identifier: 2017-599-00AU1
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

To assess the safety and tolerability of single and multiple doses of HMPL004-6599 in healthy male volunteers

Conditions

Ulcerative Colitis; Crohn Disease

Outcome Measures

Primary Outcomes (2)

• Incidence of Treatment-Emergent Adverse Events

  A primary objective of this study is to assess the safety of a single dose of up to 1800 mg in Part A (evaluated in planned steps of 600, 1200, and 1800 mg HMPL004-6599 under fed conditions of a standard meal), followed by multiple doses of up to 1800mg in Part B (evaluated in planned steps of 200mg TID, 400mg TID, 600mg BID and 600mg TID HMPL004-599 under fed conditions of a standard meal for 14 days ) in healthy male volunteers. The occurrence of Serious Adverse Events and Adverse Events will be evaluated during the study in order to determine this primary objective.

  Part A: single dose; Part B: 21 days

• Incidence of Participants with Abnormal Laboratory Values

  A further primary objective of this study is to assess the tolerability of a single dose of up to 1800 mg in Part A (evaluated in planned steps of 600, 1200, and 1800 mg HMPL004-6599 under fed conditions of a standard meal), followed by multiple doses of up to 1800mg in Part B (evaluated in planned steps of 200mg TID, 400mg TID, 600mg BID and 600mg TID HMPL004-599 under fed conditions of a standard meal for 14 days ) in healthy male volunteers. The occurrence of abnormal laboratory values will be reviewed during the study in order to determine this primary objective.

  Part A: single dose; Part B: 21 days

Secondary Outcomes (10)

• Maximum Plasma Concentration [Cmax]

  Part A: single dose; Part B: 21 days

• Area Under The Concentration Time Curve Up To The Time 't' [AUC0-t]

  Part A: single dose; Part B: 21 days

• Time of Maximum Plasma Drug Concentration [Tmax]

  Part A: single dose; Part B: 21 days

• Area Under The Concentration Time Curve Up To The Last Data Point Above LOQ [AUClast]

  Part A: single dose; Part B: 21 days

• Apparent Half-Life For Designated Elimination Phases [t1/2]

  Part A: single dose; Part B: 21 days

Study Arms (2)

Part A: experimental

EXPERIMENTAL

Subjects will receive HMPL004-6599 or matching placebo on Day 1. This will be administered under fed conditions with a standard meal, according to the randomization schedule. Dose levels may be repeated, or reduced if deemed appropriate by the Safety Monitoring Committee (SMC).

Drug: HMPL004-6599

Part A: placebo

PLACEBO COMPARATOR

Subjects will receive matching placebo on Day 1. This will be administered under fed conditions with a standard meal, according to the randomization schedule.

Drug: Placebo

Interventions

HMPL004-6599 DRUG

For each cohort, 6 subjects will receive HMPL004-6599

Part A: experimental

Placebo DRUG

For each cohort, 2 subjects will receive placebo

Part A: placebo

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: Healthy male subjects aged 18 to 45 years of age inclusive at the time of screening.
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Informed consent must be obtained in writing for all subjects before enrollment into the study.
• Healthy male subjects aged 18 to 45 years inclusive at the time of screening.
• Body mass index ≥19.0 and ≤ 30.0 kg/m2
• No clinically significant abnormalities as determined by medical history and physical examination, especially with regard to the liver, bile and gastrointestinal systems.
• No clinically significant laboratory values and urinalysis, as determined by the Clinical Investigator.
• No clinically significant findings in ECG, blood pressure and heart rate, as determined by the Clinical Investigator.
• Willing to comply with the contraceptive requirements of the study and must not donate sperm during the study and for 3 months afterwards. Subjects must agree to use a condom or to abstain from sexual intercourse throughout the trial and for 3 months afterwards.

You may not qualify if:

• Subjects presenting with any of the following will not be included in the study:
• Family history of premature Coronary Heart Disease
• History of immunosuppression or opportunistic infections or receipt of a live virus vaccination within the 3 months prior to screening.
• Subjects at risk for tuberculosis (TB), specifically subjects with:
• Clinical or laboratory evidence of active TB
• History of active TB unless there is documentation that the prior anti-TB treatment was appropriate in duration and type
• Latent TB which has not been successfully treated
• History of hypertension requiring treatment.
• Any condition requiring the regular use of any medication.
• Exposure to prescription medications within 30 days prior to Day 1.
• Exposure to any other medication, including over-the counter medications, herbal remedies and vitamins 14 days prior to first dose (except for paracetamol).
• Treatment in the previous 3 months with any drug known to have a well-defined potential for toxicity to a major organ. Once-off medication such as paracetamol or any medication deemed not clinically significant by the principal investigator can be permitted.
• Current smoker of more than 10 cigarettes or equivalent / day during past 3 months prior to commencing the study and unable to completely stop smoking during the study.
• Symptoms of a clinically significant illness in the 3 months before the study.
• Presence or sequelae of gastrointestinal, liver or kidney disease, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs.

Sponsors & Collaborators

• Nutrition Science Partners Limited: lead
• Hutchison Medipharma Limited: collaborator
• Société des Produits Nestlé (SPN): collaborator

Study Sites (1)

Linear Clinical Research

Perth, Western Australia, Australia

Location

MeSH Terms

Conditions

Colitis, Ulcerative; Crohn Disease

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Study Officials

• Wu Yan, MD

  Hutchison Medipharma Limited

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Double blind, randomized, placebo-controlled, dose-escalating, single dose study in healthy volunteers followed by a double blind, randomized, placebo-controlled, dose-escalating, multiple dose study in healthy volunteers.

Study Record Dates

• First Submitted: May 3, 2018
• First Posted: July 24, 2018
• Study Start: March 20, 2018
• Primary Completion: November 19, 2018
• Study Completion: November 19, 2018
• Last Updated: December 17, 2019

Record last verified: 2019-12

Locations

AU (1)