Rheumatoid Arthritis (RA)Phase 1NCT02105129
A Study of the Safety, Tolerability and Pharmacokinetics of HMPL-523
A Phase 1 study testing HMPL-523 in people with Rheumatoid Arthritis (RA), run by Hutchison Medipharma Limited at 1 site in Australia.
Trial summary
The primary objective of this study is to assess the safety and tolerability of a single dose of up to 800 mg in Part A (evaluated in planned steps of 5, 20, 50, 100, 200, 300 mg under fasted conditions, followed by 300, 400, 600 and 800 mg HMPL-523 under fed conditions of a standard meal, followed by multiple doses… Read more about this study
- Who is it for?
- Ages 18 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Rheumatoid Arthritis (RA)
- What is being tested?
- HMPL-523
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 118 participants
- Where
- 1 siteAustralia
- Study dates
- May 2014to Dec 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Informed consent must be obtained in writing for all subjects before enrollment into the study
- Healthy male subjects aged 18 to 45years 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 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.
Who cannot join
- Family history of premature Coronary Heart Disease
- Any condition requiring the regular use of any medication
- Exposure to prescription medications or to drugs known to interfere with metabolism of drugs 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
- Participation in another study with any investigational drug in the 30 days preceding Day 1 of the study
- Treatment in the previous 3 months with any drug known to have a well defined potential for toxicity to a major organ
Show all 21Show fewer
- Current smoker of more than 10 cigarettes or equivalent / day prior to commencing the study and unable to completely stop smoking during the study
- Be in the exclusion period of any previous study with investigational drugs
- 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
- Chronic constipation or diarrhea, irritable bowel syndrome, inflammatory bowel disease, Hemorrhoids or anal diseases with regular or recent presence of blood in feces
- History of significant allergic disease (e.g. Allergic to medications) and acute phase of allergic rhinitis in the previous 2 weeks before randomization or any food allergy
- Blood or plasma donation of more than 500 ml during the previous 30 Days before randomization and/or more than 50 ml in the 2 weeks prior to screening
- Known positive test for HIV
- Known positive test for hepatitis B or C, unless caused by immunization
- Current evidence of drug abuse or history of drug abuse within one year before randomization
- History of alcohol abuse or active alcoholism as defined in Appendix A Definition of alcohol abuse
- Mental condition rendering the subject incapable to understand the nature, scope, and possible consequences of the study
- Adults under guardianship and people with restriction of freedom by administrative or legal decisions
- 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
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I, Randomized, Double Blind, Placebo-controlled, Dose-escalating Study of the Safety, Tolerability and Pharmacokinetics of Single and Repeat Doses of HMPL-523
The primary objective of this study is to assess the safety and tolerability of a single dose of up to 800 mg in Part A (evaluated in planned steps of 5, 20, 50, 100, 200, 300 mg under fasted conditions, followed by 300, 400, 600 and 800 mg HMPL-523 under fed conditions of a standard meal, followed by multiple doses of 200, 300, 400 and 500 mg of HMPL-523 in Part B, in healthy male volunteers.
The secondary objective is to determine the pharmacokinetic profile of single (Part A) and multiple (Part B) oral doses of HMPL-523 in healthy male volunteers and to determine the preliminary effect of food (Part C）
Read the detailed description
This is a Phase I study with 3 parts:
Part A: Double blind, randomized, placebo-controlled, dose-escalating, single dose study in healthy volunteers.
Part B: Double blind, randomized, placebo-controlled, dose-escalating, multiple dose study in healthy volunteers.
Part C: Open labeled, single dose, cross-over, preliminary food effect study in healthy volunteers.
Number of subjects:
Part A: 80 healthy volunteers (10 cohorts of 8 subjects) Part B: About 40 healthy volunteers (5 cohorts of 8 subjects) In Part B, the multiple doses are 200(Cohort B1), 300(Cohort B2), 400(Cohort B3), and 500 mg(Cohort B4) and 8 subjects will be enrolled in each cohort. At dose 200mg, additional cohort (Cohort B1a) with 8 subjects needs to be enrolled based on the clinical data (safety, tolerability, available PK data and clinical laboratory values). The decision is made jointly by the Principal Investigator and the sponsor. Within each cohort, 6 subjects will receive HMPL-523 and 2 subjects will receive placebo Part C: 6 healthy volunteers (1 cohort; all will receive HMPL-523 100 mg).
Treatments:
-Part A: Single Ascending Dose.Subjects will receive a single dose of up to 800 mg HMPL-523 or matching placebo during Day 1. The planned dose levels are: 5, 20, 50,100, 200, 300 mg under fasted conditions, followed by 300, 400, 600, 800 mg under fed conditions with a standard meal, according to the randomization schedule. Dose levels may be repeated, reduced or administered as a split dose if deemed appropriate by the Principal Investigator and Sponsor's medical Expert.
For Cohort 1 a sentinel group (1 HMPL-523 and 1 placebo) will be dosed at 5 mg HMPL-523, 24 hours prior to the planned dosing of the remaining six subjects. Dosing of the remaining six will be based on investigator judgment. The decision to dose escalate 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).
-Part B: Multiple Ascending Dose (MAD). Part B of the study has been designed to assess the effects of multiple ascending doses of HMPL-523 in healthy volunteers. The total daily doses and dosing regimen for Part B have been determined as 200, 300,400 and 500 mg based on the review of safety and PK data from Part A, made jointly by the Principal Investigator and the sponsor. The dose will be the same or less than one already administered to participants in Part A. Because dog has similar protein binding to humans, we will closely monitor the clinical safety and laboratory result when the AUC is getting to 2085 h*ng/mL, which is the NOAEL AUC in dogs. Further dose escalation will be based on clinical safety and discussion between the sponsor and the investigators.
Part C: Preliminary Food Effect Study. Part C of the study has been designed to preliminarily assess the effect of food on the pharmacokinetics of HMPL-523 in healthy volunteers. Subjects will first receive a single dose of HMPL-523 100mg under fasted conditions (Period 1) and then following a washout period of 7 days, will receive a single dose of HMPL-523 100mg after consuming a standard high fat breakfast (fed conditions) (Period 2). Part C may be conducted at any time, provided 100 mg has been deemed safe in Part A.
Safety data:
The following safety evaluations will be performed during the study: Adverse events, physical examination, clinical safety laboratory (hematology, clinical chemistry, urinalysis), body weight, oral temperature, triplicate blood pressure and heart rate , and ECG .
- Conditions
- Rheumatoid Arthritis (RA)
- Being tested
- HMPL-523, Placebo
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HMPL-523Drug
Also called HMPL-523 acetate
HMPL-523: Oral administration with a single dose of 5, 20, 50, 100, 200 and 300 mg in Part A, followed by multiple doses of selected strength in Part B Other Name: NA
PlaceboDrug
Also called HMPL-523 Placebo
Oral administration
| Study group | Role | What they receive |
|---|---|---|
| HMPL-523 | Experimental | Single/Multiple Ascending Dose. oral administration, a single dose of 5, 20, 50, 100, 200 and 300 mg (Part A) and multiple dose of HMPL-523 at dose level based on result of Part A Receives: Drug: HMPL-523 |
| Placebo | Placebo comparator | Placebo: oral administration Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess number of participants with adverse events as a measure of safety and tolerability during dose escalating
Measured: 6 months
Secondary outcomes (1)
To measure the plasma concentration of HMPL-523 in single and repeated doses
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2014 (estimated)
- Study startMay 2014
- Primary completionDec 2015
- Study completionDec 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Rheumatoid Arthritis (RA)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 118 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hutchison Medipharma Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jason Lickliter, MD, Principal investigator, Nucleus Network LtdYan Wu, MD, Study director, Hutchison Medipharma Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02105129
- Sponsor's protocol ID
- 2014-523-00AU1
- Status last verified
- Apr 2016
- First submitted
- 19 Mar 2014
- Last updated
- 28 Apr 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Randomized, Double Blind, Placebo-controlled, Dose-escalating Study of the Safety, Tolerability and Pharmacokinetics of Single and Repeat Doses of HMPL-523
- ClinicalTrials.gov ID
- NCT02105129
- Acronym / sponsor ID
- 2014-523-00AU1
- Conditions
- Rheumatoid Arthritis (RA)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 118 participants (actual)
- Lead sponsor
- Hutchison Medipharma LimitedIndustry (pharma, biotech, devices)
- Study start
- May 2014
- Primary completion
- Dec 2015 (actual)
- Study completion
- Dec 2015 (actual)
- First posted
- 7 Apr 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objective of this study is to assess the safety and tolerability of a single dose of up to 800 mg in Part A (evaluated in planned steps of 5, 20, 50, 100, 200, 300 mg under fasted conditions, followed by 300, 400, 600 and 800 mg HMPL-523 under fed conditions of a standard meal, followed by multiple doses of 200, 300, 400 and 500 mg of HMPL-523 in Part B, in healthy male volunteers.
The secondary objective is to determine the pharmacokinetic profile of single (Part A) and multiple (Part B) oral doses of HMPL-523 in healthy male volunteers and to determine the preliminary effect of food (Part C）
Detailed description
This is a Phase I study with 3 parts:
Part A: Double blind, randomized, placebo-controlled, dose-escalating, single dose study in healthy volunteers.
Part B: Double blind, randomized, placebo-controlled, dose-escalating, multiple dose study in healthy volunteers.
Part C: Open labeled, single dose, cross-over, preliminary food effect study in healthy volunteers.
Number of subjects:
Part A: 80 healthy volunteers (10 cohorts of 8 subjects) Part B: About 40 healthy volunteers (5 cohorts of 8 subjects) In Part B, the multiple doses are 200(Cohort B1), 300(Cohort B2), 400(Cohort B3), and 500 mg(Cohort B4) and 8 subjects will be enrolled in each cohort. At dose 200mg, additional cohort (Cohort B1a) with 8 subjects needs to be enrolled based on the clinical data (safety, tolerability, available PK data and clinical laboratory values). The decision is made jointly by the Principal Investigator and the sponsor. Within each cohort, 6 subjects will receive HMPL-523 and 2 subjects will receive placebo Part C: 6 healthy volunteers (1 cohort; all will receive HMPL-523 100 mg).
Treatments:
-Part A: Single Ascending Dose.Subjects will receive a single dose of up to 800 mg HMPL-523 or matching placebo during Day 1. The planned dose levels are: 5, 20, 50,100, 200, 300 mg under fasted conditions, followed by 300, 400, 600, 800 mg under fed conditions with a standard meal, according to the randomization schedule. Dose levels may be repeated, reduced or administered as a split dose if deemed appropriate by the Principal Investigator and Sponsor's medical Expert.
For Cohort 1 a sentinel group (1 HMPL-523 and 1 placebo) will be dosed at 5 mg HMPL-523, 24 hours prior to the planned dosing of the remaining six subjects. Dosing of the remaining six will be based on investigator judgment. The decision to dose escalate 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).
-Part B: Multiple Ascending Dose (MAD). Part B of the study has been designed to assess the effects of multiple ascending doses of HMPL-523 in healthy volunteers. The total daily doses and dosing regimen for Part B have been determined as 200, 300,400 and 500 mg based on the review of safety and PK data from Part A, made jointly by the Principal Investigator and the sponsor. The dose will be the same or less than one already administered to participants in Part A. Because dog has similar protein binding to humans, we will closely monitor the clinical safety and laboratory result when the AUC is getting to 2085 h*ng/mL, which is the NOAEL AUC in dogs. Further dose escalation will be based on clinical safety and discussion between the sponsor and the investigators.
Part C: Preliminary Food Effect Study. Part C of the study has been designed to preliminarily assess the effect of food on the pharmacokinetics of HMPL-523 in healthy volunteers. Subjects will first receive a single dose of HMPL-523 100mg under fasted conditions (Period 1) and then following a washout period of 7 days, will receive a single dose of HMPL-523 100mg after consuming a standard high fat breakfast (fed conditions) (Period 2). Part C may be conducted at any time, provided 100 mg has been deemed safe in Part A.
Safety data:
The following safety evaluations will be performed during the study: Adverse events, physical examination, clinical safety laboratory (hematology, clinical chemistry, urinalysis), body weight, oral temperature, triplicate blood pressure and heart rate , and ECG .
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HMPL-523 | Experimental | Drug: HMPL-523Single/Multiple Ascending Dose. oral administration, a single dose of 5, 20, 50, 100, 200 and 300 mg (Part A) and multiple dose of HMPL-523 at dose level based on result of Part A |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo: oral administration |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Informed consent must be obtained in writing for all subjects before enrollment into the study
- Healthy male subjects aged 18 to 45years 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.
Key exclusion criteria (21 listed)
- Family history of premature Coronary Heart Disease
- Any condition requiring the regular use of any medication
- Exposure to prescription medications or to drugs known to interfere with metabolism of drugs 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
- Participation in another study with any investigational drug in the 30 days preceding Day 1 of the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HMPL-523Also: HMPL-523 acetateHMPL-523: Oral administration with a single dose of 5, 20, 50, 100, 200 and 300 mg in Part A, followed by multiple doses of selected strength in Part B Other Name: NA | Drug | HMPL-523 |
| PlaceboAlso: HMPL-523 PlaceboOral administration | Drug | Placebo |
Primary outcome
To assess number of participants with adverse events as a measure of safety and tolerability during dose escalating
Time frame: 6 months
1 secondary outcome
To measure the plasma concentration of HMPL-523 in single and repeated doses
Time frame: 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jason Lickliter, MD principal investigator
Nucleus Network Ltd
Yan Wu, MD study director
Hutchison Medipharma Limited
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing HMPL-523 in people with Rheumatoid Arthritis (RA), run by Hutchison Medipharma Limited at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To assess number of participants with adverse events as a measure of safety and tolerability during dose escalating (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Apr 2016.