A Study to Evaluate the One-way Interaction of Calcium Carbonate, Omeprazole, or Rifampin on ACP-196

Healthy Participants Clinical Trial

Official title:

A Phase 1, Single-Center, Open-Label, Fixed-Sequence, 2-Period, 3-Part Study to Evaluate the One-Way Interaction of Calcium Carbonate, Omeprazole, or Rifampin on ACP-196 in Healthy Adult Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04914936
• Other study ID #: ACE-HV-004
• Status: Completed
• Phase: Phase 1
• Start date: September 21, 2014
• Est. completion date: October 16, 2014

Study information

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

Clinical Trial Summary

The study will evaluate one-way interaction of calcium carbonate, omeprazole, or rifampin on ACP-196.

Description:

This is a 3-part study. Each part will be conducted as an open-label, 2-period, fixed-sequence study. All the study parts will be conducted concurrently and the participants will receive the study treatment in all the parts after an overnight fast. In each part, 24 healthy, non-tobacco using, men and women will be enrolled, to ensure 22 participants complete each part. Each participant will participate in only one study part. In Part 1, a single oral dose of ACP-196 100 mg capsule will be administered on Day 1 of Period 1 (Treatment A), and a single oral dose of calcium carbonate 1 g tablets will be coadministered with a single oral dose of ACP-196 100 mg on Day 1 of Period 2 (Treatment B). In Part 2, a single oral dose of ACP-196 100 mg capsule will be administered on Day 1 pf Period 1 (Treatment C) and oral doses of omeprazole 40 mg capsules once daily (QD) for 5 consecutive days with a single oral dose of ACP-196 100 mg capsule coadministered on Day 5 of Period 2 (Treatment D). In Part 3, a single oral dose of ACP-196 will be administered on Day 1 of Period 1 (Treatment E) and oral dose of rifampin 600 mg capsule QD for 9 consecutive days with a single oral dose of ACP-196 100 mg capsule coadministered on Day 1 and Day 9. Participants will be screened within 28 days before the dose. There will be no washout between the dose in Period 1 and the first dose in Period 2. Participants will be contacted approximately 14 days after the last dose of study drug for adverse events.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 72
• Est. completion date: October 16, 2014
• Est. primary completion date: October 16, 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Continuous non-smoker who has not used nicotine-containing products for at least 3 months prior to the first dose.
• Body mass index (BMI) >= 18.0 and =< 32.0 kg/m^2 at screening.
• Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or electrocardiograms (ECGs), as deemed by the principal investigator (PI). Liver function tests must be =< upper limit of normal range (ULN).
• Women must be of non-childbearing status and must have negative serum pregnancy test results.
• Men of reproductive potential to follow protocol defined contraception methods.
• Able to swallow multiple capsules.

Exclusion Criteria:

• Participant is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study.
• History or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI.
• History of any illness that, in the opinion of the PI, might confound the results of the study or poses an additional risk to the participant by their participation in the study.
• Presence of any clinically significant, ongoing systemic bacterial, fungal, or viral infections in the opinion of the PI.
• History or presence of alcoholism or drug abuse within the past 2 years prior to screening.
• Women who are pregnant or lactating.
• Positive urine drug or alcohol results at screening or check-in.
• Positive urine cotinine at screening.
• Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV).
• Seated blood pressure is less than 90/40 mm Hg or greater than 140/90 mmHg at screening.
• Seated heart rate is lower than 40 beats per minute (bpm) or higher than 99 bpm at screening.
• Hemoglobin level below the lower limit of normal at screening.
• Have been on a diet incompatible with the on-study diet, in the opinion of the PI, within the 28 days prior to the first dose of study drug, and throughout the study.
• Unable to refrain from or anticipates the use of any protocol defined drugs.
• Donation of blood or significant blood loss within 56 days prior to the first dose of study drug.
• Plasma donation within 7 days prior to the first dose of study drug.

Part 1 Only:

• History or presence of clinically significant hypersensitivity or idiosyncratic reaction to ACP-196, calcium carbonate, related compounds, or any inactive ingredients.
• History or presence of liver disease.

Part 2 Only:

• History or presence of clinically significant hypersensitivity or idiosyncratic reaction to ACP-196, omeprazole, related compounds or any inactive ingredients.
• History or presence of liver disease; Clostridium difficile-associated diarrhea.

Part 3 Only:

• History or presence of clinically significant hypersensitivity or idiosyncratic reaction to ACP-196, rifampin, related compounds, or any inactive ingredients.
• History or presence of liver disease; diabetes mellitus.
• Estimated creatinine clearance < 90 mL/min at screening.

Related Conditions & MeSH terms

• Healthy Participants

Intervention

Drug:
• ACP-196
Participants will receive a single oral dose of ACP-196 100 mg capsule on Day 1 of Period 1 in Part 1, Part 2, and Part 3; and on Day 1 of Period 2 in Part 1, Day 5 of Period 2 in Part 2, and Day 1 and Day 9 of Period 2 in Part 3.
• Calcium carbonate
Participants will receive a single oral dose of calcium carbonate 1 g tablet on Day 1 of Period 2 in Part 1.
• Omeprazole
Participants will receive multiple oral doses of omeprazole 40 mg capsules QD for 5 consecutive days in Period 2 of Part 2.
• Rifampin
Participants will receive multiple oral doses of rifampin 600 mg capsule QD for 9 consecutive days in Period 2 of Part 3.

Locations

Country	Name	City	State
n/a

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 Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of ACP-196 in Parts 1, 2, and 3		Period 1: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 hrs on Day 1 for all parts; Period 2: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 hrs on Day 1 for Part 1, on Day 5 for Part 2, and on Days 1 and 9 for Part 3
Primary	Maximum Observed Plasma Concentration (Cmax) of ACP-196 in Parts 1, 2, and 3		Period 1: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 hrs on Day 1 for all parts; Period 2: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 hrs on Day 1 for Part 1, on Day 5 for Part 2, and on Days 1 and 9 for Part 3
Secondary	Area Under the Plasma Concentration-time Curve From Time 0 to Time of Last Measurable Concentration (AUC0-last) of ACP-196 in Parts 1, 2, and 3		Period 1: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 hrs on Day 1 for all parts; Period 2: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 hrs on Day 1 for Part 1, on Day 5 for Part 2, and on Days 1 and 9 for Part 3
Secondary	Percent of AUC0inf Extrapolated (AUC%extrap) of ACP-196 in Parts 1, 2, and 3		Period 1: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 hrs on Day 1 for all parts; Period 2: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 hrs on Day 1 for Part 1, on Day 5 for Part 2, and on Days 1 and 9 for Part 3
Secondary	Area Under the Plasma Concentration-time Curve From Time 0 to 24 hours (AUC0-24h) of ACP-196 in Parts 1, 2, and 3		Period 1: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 hrs on Day 1 for all parts; Period 2: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 hrs on Day 1 for Part 1, on Day 5 for Part 2, and on Days 1 and 9 for Part 3
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax) of ACP-196 in Parts 1, 2, and 3		Period 1: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 hrs on Day 1 for all parts; Period 2: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 hrs on Day 1 for Part 1, on Day 5 for Part 2, and on Days 1 and 9 for Part 3
Secondary	Apparent Terminal Elimination Half-life (T1/2) of ACP-196 in Parts 1, 2, and 3		Period 1: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 hrs on Day 1 for all parts; Period 2: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 hrs on Day 1 for Part 1, on Day 5 for Part 2, and on Days 1 and 9 for Part 3
Secondary	Apparent Terminal Elimination Rate Constant (?z) of ACP-196 in Parts 1, 2, and 3		Period 1: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 hrs on Day 1 for all parts; Period 2: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 hrs on Day 1 for Part 1, on Day 5 for Part 2, and on Days 1 and 9 for Part 3
Secondary	Apparent Total Body Clearance (CL/F) of ACP-196 in Parts 1, 2, and 3		Period 1: 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 hrs on Day 1 for all parts; Period 2: 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, 24 hrs on Day 1 for Part 1, on Day 5 for Part 2, and on Days 1 and 9 for Part 3
Secondary	Incidence of Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events in Parts 1, 2, and 3		From Day 1 through 14 days after the last dose (approximately 1 month) in all 3 parts
Secondary	Number of Participants With Abnormal Physical Examinations and Vital Signs Reported as TEAEs in Parts 1, 2, and 3		Part 1: Day 1; Part 2: Day 1 through Day 5; Part 3: Day 1 through Day 9
Secondary	Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Parts 1, 2, and 3		Part 1: Day 1; Part 2: Day 1 through Day 5; Part 3: Day 1 through Day 9
Secondary	Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Parts 1, 2, and 3		Part 1: Day 1; Part 2: Day 1 through Day 5; Part 3: Day 1 through Day 9