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AzTrials

Rheumatoid ArthritisPhase 1NCT01765478

Safety,PK/PD, Food Effect Study of Orally Administered HM71224 in Healthy Adult Male Volunteers

A Phase 1 study testing HM71224 single ascending dose, HM71224 food effect and HM71224 Multiple ascending dose in people with Rheumatoid Arthritis, run by Hanmi Pharmaceutical Company Limited at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

HM71224 is a potent small molecule inhibitor of Bruton's tyrosine kinase (BTK). BTK is a member of the Tec family of non-receptor protein tyrosine kinases. BTK is mostly expressed in hematopoietic cells such as B cells, mast cells and macrophages. Read more about this study

Who is it for?
Ages 18 to 65 years, men onlyHealthy volunteers can take part
Conditions the study is for
Rheumatoid Arthritis
What is being tested?
HM71224 single ascending dose, HM71224 food effect and HM71224 Multiple ascending dose
Could I receive a placebo?
No, everyone receives an active treatment
How many people
62 participants
Where
1 siteNetherlands
Study dates
Jan 2013to Nov 2014
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 65 years
  • Men only
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Gender : male
  • Age : 18-65 years, inclusive
  • BMI : 18.5 - 30.0 kg/m2
  • Ability and willingness to abstain from alcohol, methylxanthine-containing beverages or food (coffee, tea, cola, chocolate, energy drinks), and grapefruit (juice) from 48 h prior to entry in the clinical research center until discharge
  • Medical history without major pathology
  • Normal resting supine blood pressures and pulse rate, showing no clinically relevant deviations as judged by the MI
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  • Computerized (12-lead) electrocardiogram (ECG) recording without signs of clinically relevant pathology or showing no clinically relevant deviations as judged by the MI
  • Willingness to use adequate contraception from the time of dosing until 90 days after the follow-up visit
  • All values for hematology and for clinical chemistry tests of blood and urine within the normal range or showing no clinically relevant deviations as judged by the MI
  • Willingness to sign the written Informed Consent Form (ICF)

Who cannot join

  • Previous participation in the current study
  • Evidence of clinically relevant pathology
  • Mental handicap
  • History of relevant drug and/or food allergies
  • Regular/routine treatment with non-topical medications within 30 days prior to entry into the clinical research center
  • Use of tobacco products within 60 days prior to drug administration
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  • History of alcohol abuse or drug addiction (including soft drugs like cannabis products)
  • Use of concomitant medication, except for acetaminophen (paracetamol), which is allowed up to 3 days before entry into the clinical research center. Multivitamins and vitamin C are allowed up to 7 days before entry into the clinical research center. All other medication (including over the counter medication, health supplements, and herbal remedies such as St. John's Wort extract) must have been stopped at least 14 days prior to entry into the clinical research center. The use of a limited amount of acetaminophen during the study is permitted.
  • Participation in a drug study within 60 days prior to drug administration. Participation in more than 3 other drug studies in the 10 months preceding the start of this study (this is the first administration of study drug).
  • Donation of more than 50 mL of blood within 60 days prior to drug administration. Donation of more than 1.5 liters of blood in the 10 months preceding the start of this study (this is the first administration of study drug).
  • Positive drug screen (opiates, methadone, cocaine, amphetamines, cannabinoids, barbiturates, benzodiazepines, and alcohol)
  • Intake of more than 24 units of alcohol per week (one unit of alcohol equals approximately 250 mL of beer, 100 mL of wine or 35 mL of spirits)
  • Positive screen on Hepatitis B Surface Antigen (HBsAg), anti-Hepatitis C Virus (HCV) or anti-Human Immunodeficiency Virus (HIV) 1/2
  • Illness within 5 days prior to the first drug administration
  • Non-willingness to consume the FDA breakfast (Part B only)

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

  • PRA Clinical research center

    Zuidlaren

Other trials in Netherlands

About this study

Official title: A Phase1 Study, to Determine the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of Single and Multiple Doses of Orally Administered HM71224 in Healthy, Adult Male Volunteers

HM71224 is a potent small molecule inhibitor of Bruton's tyrosine kinase (BTK). BTK is a member of the Tec family of non-receptor protein tyrosine kinases. BTK is mostly expressed in hematopoietic cells such as B cells, mast cells and macrophages. BTK plays key roles in multiple cell signaling pathways including B-Cell Receptor (BCR) and Fc receptor (FcR) signaling cascades and is an essential mediator not only in B-cell dependent but also in myeloid cell dependent inflammatory arthritis. HM71224 has been selected as a novel therapeutic agent for the treatment of autoimmune diseases such as rheumatoid arthritis (RA).

In view of the above, further development of HM71224 for the treatment of RA is warranted. In this first-in-man (FIM) study, a single and multiple dose escalation design will be employed, in which the primary objective is to evaluate the safety and tolerability of the compound. The biomarkers included as pharmacodynamic (PD) variables are chosen as they are indicators for any effects of HM71224 on the expected mode of action (pBTK, pPLCγ, and pERK).

Read the detailed description

Primary objective

  • To evaluate the safety and tolerability, and if possible maximum tolerated dose (MTD) of HM71224 after single and multiple ascending dose administration in healthy subjects.

Secondary objective

  • To determine the PK of HM71224 and selected metabolites (M1 and M2) following single and multiple oral dose administration of HM71224.
  • To assess the PD effects of HM71224 on the biomarkers pBTK, pPLCγ, and pERK.
  • To assess whether the PK of HM71224 is affected by food.
Being tested
HM71224 single ascending dose, HM71224 food effect, HM71224 Multiple ascending dose
Keywords
Rheumatoid Arthritis
Medical subject headings
Arthritis, Rheumatoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HM71224 single ascending doseDrug

  • HM71224 food effectDrug

  • HM71224 Multiple ascending doseDrug

Study groups in NCT01765478
Study groupRoleWhat they receive
Treatment A Period 2Experimental40mg HM71224 single dose
Receives: Drug: HM71224 single ascending dose
Treatment B Period1Experimental20mg HM71224 single dose
Receives: Drug: HM71224 single ascending dose
Treatment A Period1Experimental10mg HM71224 single dose
Receives: Drug: HM71224 single ascending dose
Treatment B Period2Experimental80mg HM71224 single dose
Receives: Drug: HM71224 single ascending dose
TreatmentA Period3Experimental160mg HM71224 single dose
Receives: Drug: HM71224 single ascending dose
TreatmentB Period3Experimental200mg HM71224 single dose
Receives: Drug: HM71224 single ascending dose
Food effect period1Experimentalactive 4subjects + placebo 4subjects
Receives: Drug: HM71224 food effect
Food effect period2Experimentalactive 4subjects + placebo 4subjects
Receives: Drug: HM71224 food effect
TreatmentCExperimentalHM71224 Xmg multiple dose for 14days
Receives: Drug: HM71224 Multiple ascending dose
TreatmentDExperimentalHM71224 Ymg 14days multiple dose
Receives: Drug: HM71224 Multiple ascending dose
TreatmentEExperimentalHM71224 Zmg 14days multiple dose
Receives: Drug: HM71224 Multiple ascending dose

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To investigate safety and tolerability

    Number of participants with AE occurrence, clinically significant clinical lab,vital sign, and/or ECG change.

    Measured: 3days

Secondary outcomes (2)

  1. To determine plasma PK parameters

    Cmax, C trough, tmax, kel, t1/2, AUC, CL/F, Vz, Rac, Ae, CLr, Fe% of HM71224 and selected metabolites M1, M2 following single and multiple oral dose administration of HM71224

    Measured: 3days

  2. To determine urine PK parameters

    Cmax, C trough, tmax, kel, t1/2, AUC, %AUC, CL/F, Vz, Rac, Ae, CLr, Fe% of of HM71224 and selected metabolites M1, M2 following single and multiple oral dose administration of HM71224

    Measured: 3days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Jan 2013 (estimated)
  2. Study startJan 2013
  3. Primary completionNov 2014
  4. Study completionNov 2014

Resources

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
Double blind
Who is masked
Participant, Investigator
Enrolment
62 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01765478
Sponsor's protocol ID
12-HM71224-101
Status last verified
Nov 2012
First submitted
7 Jan 2013
Last updated
18 May 2015
Results posted
No
Data monitoring committee
No

Publications

  • Byun JY, Koh YT, Jang SY, Witcher JW, Chan JR, Pustilnik A, Daniels MJ, Kim YH, Suh KH, Linnik MD, Lee YM. Target modulation and pharmacokinetics/pharmacodynamics translation of the BTK inhibitor poseltinib for model-informed phase II dose selection. Sci Rep. 2021 Sep 21;11(1):18671. doi: 10.1038/s41598-021-98255-7.

    PubMed 34548595

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing HM71224 single ascending dose, HM71224 food effect and HM71224 Multiple ascending dose in people with Rheumatoid Arthritis, run by Hanmi Pharmaceutical Company Limited at 1 site in Netherlands.

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 10 inclusion and 15 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 18 May 2015. 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 Netherlands. 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. 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 investigate safety and tolerability (time frame: 3days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01765478, which also lists 1 linked publication.

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 18 May 2015.

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