A Study to Evaluate the Effect of an Acidic Formulation of Acalabrutinib (ACP-196), Acidic Beverage, or Grapefruit Juice on the Pharmacokinetics (PK) of ACP-196 Alone and Coadministered With Omeprazole

NCT04876807 | Completed Phase 1 FDA Drug

• 1 other identifier: ACE-HV-112
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the effect of an acidic formulation of Acalabrutinib (ACP-196), acidic beverage, or grapefruit Juice on the PK of ACP-196 alone and coadministered with omeprazole.

Conditions

Healthy Volunteers

Keywords

Acalabrutinib; ACP-196; Healthy volunteers; Pharmacokinetics; PK; Acidic Formulation; Acidic Beverage; Grapefruit Juice; Omeprazole; Fixed-sequence

Outcome Measures

Primary Outcomes (3)

• 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

  0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours on Days 1, 3, 8, and 10

• Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of ACP-196 in Parts 1, 2, and 3

  0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours on Days 1, 3, 8, and 10

• Maximum Observed Plasma Concentration (Cmax) of ACP-196 in Parts 1, 2, and 3

  0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours on Days 1, 3, 8, and 10

Secondary Outcomes (17)

• Percent of AUC0inf Extrapolated (AUC%extrap) of ACP-196 in Parts 1, 2, and 3

  0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours on Days 1, 3, 8, and 10

• Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours (AUC0-6h) of ACP-196 in Parts 1, 2, and 3

  0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours on Days 1, 3, 8, and 10

• Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours (AUC0-12h) of ACP-196 in Parts 1, 2, and 3

  0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours on Days 1, 3, 8, and 10

• Time to Reach Maximum Observed Plasma Concentration (Tmax) of ACP-196 in Parts 1, 2, and 3

  0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours on Days 1, 3, 8, and 10

• Apparent Terminal Elimination Rate Constant (λz) of ACP-196 in Parts 1, 2, and 3

  0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours on Days 1, 3, 8, and 10

Study Arms (3)

Part 1 (Acidic formulation)

EXPERIMENTAL

In Part 1 of the study, the participants will receive Dose 1 of ACP-196 (reference or acidic formulation as applicable) with 240 mL water in 4 treatment schedules on Day 1, Day 3, Day 8 (with omeprazole), and Day 10 (with omeprazole).

Drug: ACP-196; Drug: Omeprazole

Part 2 (Orange drink)

EXPERIMENTAL

In Part 2 of the study, the participants will receive Dose 1 of ACP-196 (reference formulation) with 240 mL water or acidic beverage as applicable in 4 treatment schedules on Day 1, Day 3, Day 8 (with omeprazole), and Day 10 (with omeprazole).

Drug: ACP-196; Drug: Omeprazole

Part 3 (Grapefruit juice)

EXPERIMENTAL

In Part 3 of the study, the participants will receive Dose 1 of ACP-196 (reference formulation) with 240 mL water or grapefruit as applicable in 4 treatment schedules on Day 1, Day 3, Day 8 (with omeprazole), and Day 10 (with omeprazole).

Drug: ACP-196; Drug: Omeprazole

Interventions

ACP-196 DRUG

In Parts 1, 2, and 3, participants will receive oral Dose 1 of ACP-196 (reference or acidic formulation as applicable) on Day 1, Day 3, Day 8, and Day 10.

Also known as: Acalabrutinib

Part 1 (Acidic formulation); Part 2 (Orange drink); Part 3 (Grapefruit juice)

Omeprazole DRUG

Participants will receive omeprazole in all parts as: on Day 8 and Day 10 with water in Part 1; on Day 8 with water and on Day 10 with acidic beverage in Part 2; on Day 8 with water and on Day 10 with grapefruit juice in Part 3.

Part 1 (Acidic formulation); Part 2 (Orange drink); Part 3 (Grapefruit juice)

Eligibility Criteria

• Age: 19 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Continuous non-smoker who has not used nicotine-containing products for ≥ 3 months before the first dose.
• Body mass index (BMI) \>= 18.0 and =\< 32.0 kg/m\^2 at screening.
• Men and women of reproductive potential to follow protocol defined contraception methods.
• Women must have negative serum pregnancy test results.
• Willing and able to take the study drug with 240 mL of orange drink (Part 2) or grapefruit juice (Part 3).

You may not qualify if:

• 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.
• Participant with known fruit allergies.
• History or presence of clinically significant medical or psychiatric condition or disease (eg, cardiovascular, respiratory, hepatic, gastrointestinal, renal, genitourinary, endocrine, neuromuscular, rheumatologic, oncologic, cutaneous or other disorders), 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 subject 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 before screening.
• History of bleeding diathesis (eg, hemophilia, von Willebrand disease).
• Any clinically significant condition that may affect acalabrutinib absorption in the opinion of the PI, including gastric restrictions and bariatric surgery (eg, gastric bypass).
• History or presence of clinically significant thyroid disease, in the opinion of the PI.
• Women who are pregnant or breastfeeding.
• 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 \< 90/40 mm Hg or \> 140/90 mm Hg at screening.
• Seated heart rate is lower than 40 beats per minute (bpm) or higher than 99 bpm at screening.

Sponsors & Collaborators

• Acerta Pharma BV: lead

Study Sites (1)

Laura Sterling, MD, MPH

Lincoln, Nebraska, (402) 437-483, United States

Location

MeSH Terms

Interventions

acalabrutinib; Omeprazole

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Priti Patel, MD

  Acerta Pharma BV

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 5, 2021
• First Posted: May 7, 2021
• Study Start: January 28, 2016
• Primary Completion: March 15, 2016
• Study Completion: March 15, 2016
• Last Updated: May 7, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will share
• 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.
• 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.

Locations

US (1)