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

NCT01765478 | Completed Phase 1

• 1 other identifier: 12-HM71224-101
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief 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. 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).

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (1)

• To investigate safety and tolerability

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

  3days

Secondary Outcomes (2)

• To determine plasma PK parameters

  3days

• To determine urine PK parameters

  3days

Study Arms (11)

Treatment A Period 2

EXPERIMENTAL

40mg HM71224 single dose

Drug: HM71224 single ascending dose

Treatment B Period1

EXPERIMENTAL

20mg HM71224 single dose

Drug: HM71224 single ascending dose

Treatment A Period1

EXPERIMENTAL

10mg HM71224 single dose

Drug: HM71224 single ascending dose

Treatment B Period2

EXPERIMENTAL

80mg HM71224 single dose

Drug: HM71224 single ascending dose

TreatmentA Period3

EXPERIMENTAL

160mg HM71224 single dose

Drug: HM71224 single ascending dose

TreatmentB Period3

EXPERIMENTAL

200mg HM71224 single dose

Drug: HM71224 single ascending dose

Food effect period1

EXPERIMENTAL

active 4subjects + placebo 4subjects

Drug: HM71224 food effect

Food effect period2

EXPERIMENTAL

active 4subjects + placebo 4subjects

Drug: HM71224 food effect

TreatmentC

EXPERIMENTAL

HM71224 Xmg multiple dose for 14days

Drug: HM71224 Multiple ascending dose

TreatmentD

EXPERIMENTAL

HM71224 Ymg 14days multiple dose

Drug: HM71224 Multiple ascending dose

TreatmentE

EXPERIMENTAL

HM71224 Zmg 14days multiple dose

Drug: HM71224 Multiple ascending dose

Interventions

HM71224 single ascending dose DRUG

Treatment A Period 2; Treatment A Period1; Treatment B Period1; Treatment B Period2; TreatmentA Period3; TreatmentB Period3

HM71224 food effect DRUG

Food effect period1; Food effect period2

HM71224 Multiple ascending dose DRUG

TreatmentC; TreatmentD; TreatmentE

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Hanmi Pharmaceutical Company Limited: lead

Study Sites (1)

PRA Clinical research center

Zuidlaren, Netherlands

Location

Related Publications (1)

• 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.

  PMID: 34548595 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Salah Hadi, MD MSc

  PRA Health Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2013
• First Posted: January 10, 2013
• Study Start: January 1, 2013
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: May 18, 2015

Record last verified: 2012-11

Locations

NL (1)