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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: ACP-196; Drug: Calcium carbonate; Drug: Omeprazole; Drug: Rifampin

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 72
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: ACP-196 and Calcium carbonate; Participants will receive a single oral dose of ACP-196 100 mg capsule on Day 1 of Period 1 and a single oral dose of calcium carbonate 1 g tablet coadministered with a single oral dose of ACP-196 100 mg capsule on Day 1 of Period 2.	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.; Other Names: Acalabrutinib; Drug: Calcium carbonate; Participants will receive a single oral dose of calcium carbonate 1 g tablet on Day 1 of Period 2 in Part 1.
Experimental: Part 2: ACP-196 and Omeprazole; Participants will receive a single oral dose of ACP-196 100 mg capsule on Day 1 of Period 1 and oral dose of omeprazole 40 mg capsules once daily (QD) for 5 consecutive days coadministered with a single oral dose of ACP-196 100 mg capsule on Day 5 of Period 2.	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.; Other Names: Acalabrutinib; Drug: Omeprazole; Participants will receive multiple oral doses of omeprazole 40 mg capsules QD for 5 consecutive days in Period 2 of Part 2.
Experimental: Part 3: ACP-196 and Rifampin; Participants will receive a single oral dose of ACP-196 100 mg capsule on Day 1 of Period 1 and oral dose of rifampin 600 mg capsule QD for 9 consecutive days coadministered with a single oral dose of ACP-196 100 mg capsule on Day 1 and Day 9 of Period 2.	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.; Other Names: Acalabrutinib; Drug: Rifampin; Participants will receive multiple oral doses of rifampin 600 mg capsule QD for 9 consecutive days in Period 2 of Part 3.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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
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 Outcome Measures

Outcome Measure	Time Frame
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
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
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
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
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
Apparent Terminal Elimination Rate Constant (λz) 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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Acerta Pharma BV
• Investigators: Study Director: Ahmed Hamdy, MD, Acerta Pharma BV

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2014
• Primary Completion (Actual): October 16, 2014
• Study Completion (Actual): October 16, 2014

Study Registration Dates

• First Submitted: May 21, 2021
• First Submitted That Met QC Criteria: May 31, 2021
• First Posted (Actual): June 7, 2021

Study Record Updates

• Last Update Posted (Actual): June 7, 2021
• Last Update Submitted That Met QC Criteria: May 31, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; PK; Healthy participants; Acalabrutinib; ACP-196
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Gastrointestinal Agents; Anti-Bacterial Agents; Leprostatic Agents; Cytochrome P-450 Enzyme Inducers; Calcium-Regulating Hormones and Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Antacids; Calcium; Rifampin; Calcium Carbonate; Omeprazole; Acalabrutinib
• Other Study ID Numbers: ACE-HV-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No