A Study to Evaluate Safety, Pharmacokinetics, Pharmacodynamics, Food Effects, and Drug-drug Interactions of ACP-196 in Healthy Participants

Healthy Participants Clinical Trial

Official title:

A Phase 1, Single-center, Open-label, Sequential Dose-Escalation Study of ACP-196 in Healthy Subjects to Evaluate Safety, Pharmacokinetics, Pharmacodynamics, Food Effects, and Drug-Drug Interactions

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04901923
• Other study ID #: ACE-HV-001
• Status: Completed
• Phase: Phase 1
• Start date: March 15, 2014
• Est. completion date: May 22, 2014

Study information

• Verified date: May 2021
• Source: Acerta Pharma BV
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is to evaluate the safety, pharmacokinetics/pharmacodynamics (PK/PD), food-effect, and drug-drug interaction study of ACP-196 in healthy participants.

Description:

The study is divided into 3 parts. Part 1 will include 5 cohorts (Cohorts [C] 1 to 5) and participants will receive oral ACP-196 2.5 to 50 mg twice daily (BID) and 100 mg once daily (QD) on Day 1. In Part 2 (Cohort 6), participants will receive a single oral dose of 75.0 mg QD in a fasting and a fed state, with a 7-day washout period between the 2 doses. In Part 3 (Cohort 7), participants will receive a single oral dose of 50.0 mg QD alone on Day 1 and in combination with itraconazole on Day 9. Itraconazole 200 mg will be given twice daily (12 hours apart) with meals on Days 4 to 8 and once on Day 9 with ACP-196 under a fasting state in the morning.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: May 22, 2014
• Est. primary completion date: May 22, 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Body mass index (BMI) >=18.0 and <=30.0 kg/m^2.

• Healthy as determined by medical history and physical examination.

• Nonsmoker

• Normal clinical laboratory test results and ECG, or results with minor deviations which are not considered to be clinically significant in the judgment of the investigator.

• Men of and women of childbearing potential to follow protocol defined contraception methods.

• Women must have negative urine pregnancy test.

• Willingness and ability to swallow study drug capsules.

Exclusion Criteria:

• Prior or ongoing clinically significant illness, medical condition, medical history, physical findings, ECG findings, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the subject; alter the absorption, distribution, metabolism, or excretion of the study drug; or impair the assessment of study results.

• Evidence of ongoing systemic bacterial, fungal, or viral infection (including upper respiratory tract infections).

• Women cannot be pregnant or breast feeding.

• Significant history of drug or alcohol abuse or addiction within 3 years before study screening or as evidenced by continuing medical complications of prior drug or alcohol use.

• History of blood or plasma donation within 90 days before first study drug administration.

• Currently drinking over 21 units/week of ethanol

• Drug toxicology screen positive for any prohibited drugs, illicit substances, or alcohol.

• Anticipated need for alcohol, tobacco, or any drug during the study drug administration and immediate follow-up periods.

• Relative to admission has any of the following exposures: has taken a prescription systemic medication within 14 days; has used an over-the counter systemic medication (other than acetaminophen) within 7 days; has ingested calcium supplements or calcium-containing vitamins within 7 days; has ingested grapefruit, grapefruit juice, or grapefruit-containing products within 7 days; has consumed alcohol within 48 hours; has taken acetaminophen within 24 hours.

• Positive test for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen or hepatitis B core antibody, or hepatitis C antibody.

• Unwillingness to avoid vigorous physical activity during inpatient clinic confinements.

• Part 2 only - Inability or unwillingness to eat all of the ingredients of the high-fat, high-calorie meal as specified in the protocol.

• Part 3 only - Known allergy to itraconazole or other azole compounds.

Related Conditions & MeSH terms

• Healthy Participants

Intervention

Drug:
• ACP-196
Participants will receive ACP-196 oral capsule(s) in all parts.
• Itraconazole
Participants will receive itraconazole 200 mg capsules BID from Days 4 to 8 with meals and then 200 mg capsule QD on Day 9 under fasting state.

Locations

Country	Name	City	State
United States	Celerion	Tempe	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Acerta Pharma BV

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Concentration-time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) of ACP-196 in Parts 1, 2, and 3		Part 1: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 13, 14, 15, 16, 18, 20, 24, 36, 48, 60h; Parts 2 and 3: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72h; and till 48h on Day 8 of Part 2; and till 24h on Day 9 of Part 3
Primary	Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of ACP-196 in Parts 1, 2, and 3		Part 1: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 13, 14, 15, 16, 18, 20, 24, 36, 48, 60h; Parts 2 and 3: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72h; and till 48h on Day 8 of Part 2; and till 24h on Day 9 of Part 3
Primary	Maximum Observed Plasma Concentration (Cmax) of ACP-196 in Parts 1, 2, and 3		Part 1: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 13, 14, 15, 16, 18, 20, 24, 36, 48, 60h; Parts 2 and 3: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72h; and till 48h on Day 8 of Part 2; and till 24h on Day 9 of Part 3
Primary	Time to reach Cmax (Tmax) of ACP-196 in Parts 1, 2, and 3		Part 1: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 13, 14, 15, 16, 18, 20, 24, 36, 48, 60h; Parts 2 and 3: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72h; and till 48h on Day 8 of Part 2; and till 24h on Day 9 of Part 3
Primary	Terminal-elimination Half-life (T1/2) of ACP-196 in Parts 1, 2, and 3		Part 1: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 13, 14, 15, 16, 18, 20, 24, 36, 48, 60h; Parts 2 and 3: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72h; and till 48h on Day 8 of Part 2; and till 24h on Day 9 of Part 3
Primary	Terminal-elimination Rate Constant (?z) of ACP-196 in Parts 1, 2, and 3		Part 1: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 13, 14, 15, 16, 18, 20, 24, 36, 48, 60h; Parts 2 and 3: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72h; and till 48h on Day 8 of Part 2; and till 24h on Day 9 of Part 3
Primary	Time Delay Between the Time of Dosing and the First Measurable Concentration (tlag) of ACP-196 in Parts 1, 2, and 3		Part 1: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 13, 14, 15, 16, 18, 20, 24, 36, 48, 60h; Parts 2 and 3: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72h; and till 48h on Day 8 of Part 2; and till 24h on Day 9 of Part 3
Primary	Incidences of Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)		Part 1: Day 1 through Day 3; Part 2 and Part 3: Day 1 through Day 10
Primary	Incidences of Abnormal Vital Signs Reported as TEAEs		Part 1: Day 1 ( from 1 hr predose through 1 hr postdose); Part 2: From Day 1 (1 hr predose) through Day 8 (1 hr postdose); Part 3: From Day 1 (1 hr predose) through Day 9 (1 hr postdose)
Primary	Incidences of Abnormal Clinical Laboratory Parameters Reported as TEAEs		Part 1: From Day 1 to Day 2; Part 2 and Part 3: From Day 1 to Day 10
Primary	Incidences of Abnormal Electrocardiograms (ECGs) Reported as TEAEs		Part 1: Day 1 ( from 1 hr predose through 1 hr postdose); Part 2: From Day 1 (1 hr predose) through Day 8 (1 hr postdose); Part 3: From Day 1 (1 hr predose) through Day 9 (1 hr postdose)
Secondary	Occupancy of Bruton's Tyrosine Kinase (BTK) by ACP-196 in Peripheral Blood Mononuclear Cells (PBMCs)	The BTK occupancy will be measured by BTK occupancy assay which measures percent of BTK occupied post baseline compared to the baseline, post administration of study drug. The BTK occupancy is defined as ACP-196 active-site occupancy of > 80% at 24 hours after the first dose administration.	1, 3, 12, 15, and 24 hrs after first dose on Day 1
Secondary	Effect of ACP-196 on Biologic Markers of B-cell Function	The pharmacodynamics of ACP-196 will be evaluated in cluster of differentiation (CD) 69/CD86 expression. It will be considered as complete inhibition when biological markers of B-cell function (CD69 and CD86) inhibition = 90%.	1, 3, 12, 15, and 24 hrs after first dose on Day 1