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

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified November 2012 by Hanmi Pharmaceutical Company Limited
Sponsor:
Information provided by (Responsible Party):
Hanmi Pharmaceutical Company Limited
ClinicalTrials.gov Identifier:
NCT01765478
First received: January 7, 2013
Last updated: January 9, 2013
Last verified: November 2012
  Purpose

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 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).


Condition Intervention Phase
Rheumatoid Arthritis
Drug: HM71224 single asending dose
Drug: HM71224 food effect
Drug: HM71224 Multiple ascending dose
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Hanmi Pharmaceutical Company Limited:

Primary Outcome Measures:
  • To investigate safety and tolerability [ Time Frame: 3days ] [ Designated as safety issue: Yes ]
    Number of participants with AE occurrence, clinically significant clinical lab,vital sign, and/or ECG change.


Secondary Outcome Measures:
  • To determine plasma PK parameters [ Time Frame: 3days ] [ Designated as safety issue: No ]
    Cmax, Ctrough, 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

  • To determine urine PK parameters [ Time Frame: 3days ] [ Designated as safety issue: No ]
    Cmax, Ctrough, 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


Estimated Enrollment: 62
Study Start Date: January 2013
Estimated Study Completion Date: November 2013
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment A Period 2
40mg HM71224 single dose
Drug: HM71224 single asending dose
Experimental: Treatment B Period1
20mg HM71224 single dose
Drug: HM71224 single asending dose
Experimental: Treatment A Period1
10mg HM71224 single dose
Drug: HM71224 single asending dose
Experimental: Treatment B Period2
80mg HM71224 single dose
Drug: HM71224 single asending dose
Experimental: TreatmentA Period3
160mg HM71224 single dose
Drug: HM71224 single asending dose
Experimental: TreatmentB Period3
200mg HM71224 single dose
Drug: HM71224 single asending dose
Experimental: Food effect period1
active 4subjects + placebo 4subjects
Drug: HM71224 food effect
Experimental: Food effect period2
active 4subjects + placebo 4subjects
Drug: HM71224 food effect
Experimental: TreatmentC
HM71224 Xmg multiple dose for 14days
Drug: HM71224 Multiple ascending dose
Experimental: TreatmentD
HM71224 Ymg 14days multiple dose
Drug: HM71224 Multiple ascending dose
Experimental: TreatmentE
HM71224 Zmg 14days multiple dose
Drug: HM71224 Multiple ascending dose

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.
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Gender : male
  2. Age : 18-65 years, inclusive
  3. BMI : 18.5 - 30.0 kg/m2
  4. Ability and willingness to abstain from alcohol, methylxanthine-containing beverages or food (coffee, tea, cola, chocolate, "powerdrinks"), and grapefruit (juice) from 48 h prior to entry in the clinical research center until discharge
  5. Medical history without major pathology
  6. Normal resting supine blood pressures and pulse rate, showing no clinically relevant deviations as judged by the MI
  7. Computerized (12-lead) electrocardiogram (ECG) recording without signs of clinically relevant pathology or showing no clinically relevant deviations as judged by the MI
  8. Willingness to use adequate contraception from the time of dosing until 90 days after the follow-up visit
  9. 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
  10. Willingness to sign the written Informed Consent Form (ICF)

Exclusion Criteria:

  1. Previous participation in the current study
  2. Evidence of clinically relevant pathology
  3. Mental handicap
  4. History of relevant drug and/or food allergies
  5. Regular/routine treatment with non-topical medications within 30 days prior to entry into the clinical research center
  6. Use of tobacco products within 60 days prior to drug administration
  7. History of alcohol abuse or drug addiction (including soft drugs like cannabis products)
  8. 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.
  9. 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).
  10. 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).
  11. Positive drug screen (opiates, methadone, cocaine, amphetamines, cannabinoids, barbiturates, benzodiazepines, and alcohol)
  12. 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)
  13. Positive screen on Hepatitis B Surface Antigen (HBsAg), anti-Hepatitis C Virus (HCV) or anti-Human Immunodeficiency Virus (HIV) 1/2
  14. Illness within 5 days prior to the first drug administration
  15. Non-willingness to consume the FDA breakfast (Part B only)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01765478

Locations
Netherlands
PRA Clinical research center Not yet recruiting
Zuidlaren, Netherlands
Principal Investigator: Salah Hadi, MD MSc         
Sponsors and Collaborators
Hanmi Pharmaceutical Company Limited
Investigators
Principal Investigator: Salah Hadi, MD MSc PRA International
  More Information

No publications provided

Responsible Party: Hanmi Pharmaceutical Company Limited
ClinicalTrials.gov Identifier: NCT01765478     History of Changes
Other Study ID Numbers: 12-HM71224-101
Study First Received: January 7, 2013
Last Updated: January 9, 2013
Health Authority: Netherlands: Central committee on research involving human subjects

Keywords provided by Hanmi Pharmaceutical Company Limited:
Rheumatoid Arthritis

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on September 30, 2014