A Study of HMPL-689 in Healthy Volunteers

A Phase I,Randomized,Double Blinded,Placebo-controlled,Dose-escalating Study of the Safety,Tolerability and Pharmacokinetics of HMPL-689 in Healthy Volunteers

The purpose of this study is to evaluate the safety and tolerability of a single dose of HMPL-689 in healthy volunteers To determine the pharmacokinetic profile of single oral doses of HMPL-689 in healthy volunteers

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: HMPL-689; Drug: HMPL-689 placebo

Detailed Description

Subjects will receive a single dose of HMPL-689 or matching placebo during Day 1. The planned dose levels are: 1, 2.5, 5, 10, 20, 25 and 30 mg (about 7 cohorts of 8 subjects). In each dose cohort, 8 subjects will be randomized to receive HMPL-689 (6 subjects) or placebo (2 subjects) under fed condition with a standard meal.

For the first dose Cohort (1 mg), a sentinel group of 2 subjects (1 HMPL-689 and 1 placebo) will be dosed 24 hours prior to the planned dosing of the remaining six subjects. The decision of dose escalation or study termination will be made jointly by the principal investigator and the sponsor based on the clinical data (safety, tolerability, available PK data and clinical laboratory values). Any dose level may be repeated, reduced or split into 2 doses if deemed appropriate by the Principal Investigator and Sponsor's medical Expert.

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

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3001
      • Nucleus Network

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:

1. Informed consent must be obtained in writing for all subjects before enrollment into the study
2. Healthy male subjects aged 18 to 45 years inclusive at the time of screening
3. Body mass index ≥19.0 and ≤ 30.0 kg/m2
4. Willing to comply with the contraceptive requirements of the study and must not donate sperm during the study or for 3 months afterwards. Subjects must agree to use a condom or to abstain from sexual intercourse throughout the trial and for 30 days afterwards

Exclusion Criteria:

1. Family history of premature Coronary Heart Disease
2. History of immunosuppression or opportunistic infections or receipt of a live virus vaccination within the 3 months prior to screening
3. Clinically significant abnormalities as determined by medical history physical examination, or laboratory test, especially for liver and renal function
4. Clinically significant findings in ECG, blood pressure and heart rate, as determined by the Clinical Investigator

5. Subjects at risk for tuberculosis (TB), which is defined as:

   1. Current clinical or laboratory evidence of active TB
   2. History of TB
   3. A positive QuantiFERON® test at screening or within 6 months prior to Day 1
6. Any medical condition requiring regular use of medication
7. Exposure to prescription medications within 30 days prior to Day 1
8. Exposure to any other medication, including over-the-counter medications, herbal remedies and vitamins 14 days prior to first dose (except for paracetamol)
9. Participation in another clinical trial with any investigational drug within 30 days of Day 1
10. Treatment in the previous 3 months with any drug known to have a well-defined potential for toxicity to a major organ
11. Current smoker of more than 10 cigarettes or equivalent/ day prior to commencing the study and unable to completely stop smoking during the study
12. Symptoms of a clinically significant illness in the 3 months before the study
13. Presence or sequelae of gastrointestinal, liver or kidney disease, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs
14. Chronic constipation or diarrhea, irritable bowel syndrome, inflammatory bowel disease, hemorrhoids or anal diseases with regular or recent presence of blood in feces
15. History of significant allergic disease (e.g. allergic to medications) and acute phase of allergic rhinitis in the previous 2 weeks before randomization/ enrollment or any food allergy
16. Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, or current known active infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV)
17. Current evidence of drug abuse or history of drug abuse within one year before randomization/ enrollment
18. Mental condition rendering the subject incapable to understand the nature, scope, and possible consequences of the study
19. Unlikely to comply with the clinical study protocol; e.g. uncooperative attitude, inability to return for follow-up visits, and improbability of completing the study
20. Subject is the investigator or any sub-investigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HMPL-689; Subjects will receive a single dose of HMPL-689 or matching placebo on Day 1. The planned dose levels in ascending order are: 1, 2.5, 5, 10, 20, 25 and 30 mg (7 dose cohorts with 8 subjects in each cohort). Within each cohort, randomization ratio of 3:1 is followed to dose 6 subjects with HMPL-689 and 2 subjects with placebo.	Drug: HMPL-689; selective PI3Kδ inhibitor; Other Names: Huchison Medipharma
Placebo Comparator: HMPL-689 placebo; Subjects will receive a single dose of HMPL-689 or matching placebo on Day 1. The planned dose levels in ascending order are: 1, 2.5, 5, 10, 20, 25 and 30 mg (7 dose cohorts with 8 subjects in each cohort). Within each cohort, randomization ratio of 3:1 is followed to dose 6 subjects with HMPL-689 and 2 subjects with placebo.	Drug: HMPL-689 placebo; placebo of HMPL-689; Other Names: Huchison Medipharma

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
dose limited toxicities evaluated with NCI CTCAE v4.03	Incidence of dose limited toxicities and associated dose of HMPL-689	within 28 days after the first dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
maximum plasma concentration calculated with Blood samples	Blood samples will be taken to measure the levels of study drug	within 29 days after the first dose
time to reach maximum concentration calculated with Blood samples	Blood samples will be taken to measure the levels of study drug	within 29 days after the first dose

Collaborators and Investigators

• Sponsor: Hutchison Medipharma Limited
• Investigators: Principal Investigator: Jason Lickliter, Nucleus Network Ltd

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2016
• Primary Completion (Actual): October 26, 2016
• Study Completion (Actual): February 28, 2017

Study Registration Dates

• First Submitted: December 14, 2015
• First Submitted That Met QC Criteria: December 15, 2015
• First Posted (Estimate): December 16, 2015

Study Record Updates

• Last Update Posted (Actual): August 17, 2017
• Last Update Submitted That Met QC Criteria: August 15, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Other Study ID Numbers: 2015-689-00AU2

Plan for Individual participant data (IPD)

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