HMPL004-6599 Phase I Dose-escalating Study

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03597971
• Date of registration: 03/05/2018
• Prospective Registration: No
• Primary sponsor: Nutrition Science Partners Limited
• Public title: HMPL004-6599 Phase I Dose-escalating Study
• Scientific title: A Phase I, Randomized, Double Blind, Placebo-controlled, Dose-escalating Study of the Safety, Tolerability and Pharmacokinetics of Single and Repeat Doses of HMPL004-6599 in Healthy Male Volunteers
• Date of first enrolment: March 20, 2018
• Target sample size: 32
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT03597971
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Care Provider, Investigator).
• Phase: Phase 1

Countries of recruitment

Australia

Contacts

• Name: Wu Yan, MD
• Affiliation: Hutchison Medipharma Limited

Key inclusion & exclusion criteria

Inclusion Criteria:

Subjects must meet all the following for inclusion in the trial:

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. No clinically significant abnormalities as determined by medical history and physical
examination, especially with regard to the liver, bile and gastrointestinal systems.

5. No clinically significant laboratory values and urinalysis, as determined by the
Clinical Investigator.

6. No clinically significant findings in ECG, blood pressure and heart rate, as
determined by the Clinical Investigator.

7. 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.

Exclusion Criteria:

Subjects presenting with any of the following will not be included in the study:

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. Subjects at risk for tuberculosis (TB), specifically subjects with:

1. Clinical or laboratory evidence of active TB

2. History of active TB unless there is documentation that the prior anti-TB
treatment was appropriate in duration and type

3. Latent TB which has not been successfully treated

4. History of hypertension requiring treatment.

5. Any condition requiring the regular use of any medication.

6. Exposure to prescription medications within 30 days prior to Day 1.

7. Exposure to any other medication, including over-the counter medications, herbal
remedies and vitamins 14 days prior to first dose (except for paracetamol).

8. Participation in another study with any investigational drug in the 30 days preceding
Day 1 of the study or in the exclusion period of any previous study with
investigational drugs.

9. 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.

10. 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.

11. Symptoms of a clinically significant illness in the 3 months before the study.

12. Presence or sequelae of gastrointestinal, liver or kidney disease, or other conditions
known to interfere with the absorption, distribution, metabolism, or excretion of
drugs.

13. Chronic constipation or diarrhea, irritable bowel syndrome (IBS), inflammatory bowel
disease (IBD), Hemorrhoids or anal diseases with regular or recent presence of blood
in feces.

14. 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.

15. Blood or plasma donation of no more than 470 ml during the past 30 days (equivalent to
the standard blood donation in Australia) before randomization/enrollment and/or more
than 50 ml in the 2 weeks prior to screening.

16. Known positive test for human immunodeficiency virus (HIV).

17. Known positive test for hepatitis B or C, unless caused by immunization.

18. Current evidence of drug abuse or history of drug abuse within one year before
randomization/enrollment.

19. History of alcohol abuse or active alcoholism with average weekly alcohol intake that
exceeds 21 units.

20. Mental condition rendering the subject incapable to understand the nature, scope, and
possible consequences of the study.

21. Adults under guardianship and people with restriction of freedom by administrative or
legal decisions.

22. 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.

23. 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.

24. Known allergy to plants of the Acanthaceae family.

25. Those Subjects who are Vegetarian due to the requirements of the Standard Meal.



Age minimum: 18 Years
Age maximum: 45 Years
Gender: Male

Health Condition(s) or Problem(s) studied

Crohn Disease

Ulcerative Colitis

Intervention(s)

Drug: HMPL004-6599

Drug: Placebo

Primary Outcome(s)

Incidence of Treatment-Emergent Adverse Events [Time Frame: Part A: single dose; Part B: 21 days]

Incidence of Participants with Abnormal Laboratory Values [Time Frame: Part A: single dose; Part B: 21 days]

Secondary Outcome(s)

Average Concentration [Cavg] [Time Frame: Part B: 21 days]

%_Fluctuation [Time Frame: Part B: 21 days]

Maximum Plasma Concentration [Cmax] [Time Frame: Part A: single dose; Part B: 21 days]

Area Under The Concentration Time Curve Up To The Time 't' [AUC0-t] [Time Frame: Part A: single dose; Part B: 21 days]

Area Under The Concentration-Time Curve During Once Dosing Interval [AUCTau or AUC0-_] [Time Frame: Part B: 21 days]

Time of Maximum Plasma Drug Concentration [Tmax] [Time Frame: Part A: single dose; Part B: 21 days]

Apparent Half-Life For Designated Elimination Phases [t1/2] [Time Frame: Part A: single dose; Part B: 21 days]

Minimum Observed Concentration [Cmin] [Time Frame: Part B: 21 days]

Accumulation Ratio_obs [Time Frame: Part B: 21 days]

Area Under The Concentration Time Curve Up To The Last Data Point Above LOQ [AUClast] [Time Frame: Part A: single dose; Part B: 21 days]

Secondary ID(s)

2017-599-00AU1

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Hutchison Medipharma Limited

Nestlé