Study to Assess the Bioequivalence of Acalabrutinib Tablet and Acalabrutinib Capsule

NCT04768985 | Completed Phase 1 FDA Drug

• 1 other identifier: D8223C00013
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 3

Brief Summary

This study is a multicenter, Phase I, open-label, randomized, 2-sequence, 2-treatment, 2-period, crossover, bioequivalence study with single doses of acalabrutinib administered orally in healthy participants. The study is designed to demonstrate the bioequivalence of acalabrutinib tablet (Treatment A) compared with marketed acalabrutinib capsule (Treatment B) in the fasted state.

Conditions

Bioequivalence

Keywords

Pharmacokinetics; Healthy participants; Bruton tyrosine kinase; Acalabrutinib

Outcome Measures

Primary Outcomes (3)

• Area under plasma concentration time curve from zero to infinity (AUCinf) of Acalabrutinib

  To compare the AUCinf of acalabrutinib capsule with the tablet.

  Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose

• Area under the plasma concentration time curve from zero to the last quantifiable concentration (AUClast) of Acalabrutinib

  To compare the AUClast of acalabrutinib capsule with the tablet.

  Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose

• Maximum observed plasma (peak) drug concentration (Cmax) of Acalabrutinib

  To compare the Cmax of acalabrutinib capsule with the tablet

  Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose

Secondary Outcomes (10)

• Area under plasma concentration time curve from zero to infinity (AUCinf) of ACP-5862

  Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose

• Area under the plasma concentration time curve from zero to the last quantifiable concentration (AUClast) of ACP-5862

  Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose

• Maximum observed plasma (peak) drug concentration (Cmax) of ACP-5862

  Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose

• Time to reach peak or maximum concentration (tmax) following drug administration for acalabrutinib and ACP-5862

  Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose

• Half life associated with terminal slope (λz) of a semi logarithmic concentration time curve (t½λz) for acalabrutinib and ACP-5862

  Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose

Study Arms (2)

Treatment sequence 1: Treatment AB

EXPERIMENTAL

Participants will be randomized to receive one of the two different treatment sequences. In each treatment sequence participant will receive fixed single doses of 100 mg acalabrutinib orally (Treatment A; Treatment B) in 2 treatment periods, under fasted conditions. Treatment A will include acalabrutinib tablet and Treatment B will include acalabrutinib capsule.

Drug: Treatment A: Acalabrutinib tablet; Drug: Treatment B: Acalabrutinib capsule

Treament sequence 2: Treatment BA

EXPERIMENTAL

Participants will be randomized to receive one of the two different treatment sequences. In each treatment sequence participant will receive fixed single doses of 100 mg acalabrutinib orally (Treatment B; Treatment A) in 2 treatment periods, under fasted conditions. Treatment A will include acalabrutinib tablet and Treatment B will include acalabrutinib capsule.

Drug: Treatment A: Acalabrutinib tablet; Drug: Treatment B: Acalabrutinib capsule

Interventions

Treatment A: Acalabrutinib tablet DRUG

Participants will receive fixed single doses of acalabrutinib tablet in 2 treatment periods, under fasted conditions.

Also known as: CALQUENCE

Treament sequence 2: Treatment BA; Treatment sequence 1: Treatment AB

Treatment B: Acalabrutinib capsule DRUG

Participants will receive fixed single doses of acalabrutinib capsule in 2 treatment periods, under fasted conditions.

Also known as: CALQUENCE

Treament sequence 2: Treatment BA; Treatment sequence 1: Treatment AB

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Females must have a negative pregnancy test at Screening and on admission to the study center, must not be lactating, and must be of non-childbearing potential, confirmed at Screening, by fulfilling protocol defined criteria
• Have a body mass index between 18.5 and 30 kg/m\^2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive, at Screening
• Non-smokers and those participants who have not smoked (including e cigarettes) or used nicotine products (cigarettes, pipes, cigars, chewing tobacco, nicotine patch, or any other nicotine containing products) within the 90 days prior to Screening
• Calculated creatinine clearance (CrCl) ≥ 90 mL/min as determined by Cockcroft-Gault method (using actual body weight)
• Males:
• CrCl = Weight (kg) × (140 - Age)/72 × serum creatinine (mg/dL) in mL/min
• Females:
• CrCl = Weight (kg) × (140 - Age) × 0.85/72 × serum creatinine (mg/dL) in (mL/min)

You may not qualify if:

• History or presence of any clinically significant disease (including active coronavirus disease 2019 \[COVID-19\] infection) or disorder
• History or presence of gastrointestinal, hepatic, or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
• Any clinically significant illness, medical/surgical procedure, or trauma within 30 days of the first administration of study drug
• Any clinically significant abnormalities in hematology, coagulation, clinical chemistry, or urinalysis results, at Screening and prior to first dose, as judged by the Investigator and defined as:
• (i) Hemoglobin less than lower limit of normal (ii) Absolute neutrophils less than lower limit of normal (iii) Platelets less than lower limit of normal (iv) Serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase or serum bilirubin (total bilirubin and direct bilirubin) \> upper limit of normal
• Any clinically significant abnormal findings in vital signs at Screening or on Day 1 (eg, systolic BP \< 90 mmHg or \> 140 mmHg; diastolic BP \< 50 mmHg or \> 90 mmHg; pulse \< 45 or \> 90 bpm)
• Any clinically significant abnormalities on standard 12-lead ECG at Screening or on Day 1
• Any positive result for HBsAg, hepatitis C antibody, and HIV testing, at Screening
• History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, or history of hypersensitivity to drugs with a similar chemical structure or class to acalabrutinib
• Positive screen for drugs of abuse or cotinine and alcohol, at Screening and on admission to the study center
• Treatment with prescription or non-prescription drugs or other products known to be strong CYP3A, P-gp, or breast cancer resistance protein (BCRP) inhibitors or substrates of BCRP or MATE1 (within 14 days before first administration of study drug or longer if the medication has a long half life) and strong CYP3A inducers (within 28 days before first administration of study drug or longer if the medication has a long half life)
• Use of any prescribed or non prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose), and minerals during the 14 days prior to the first administration of study drug or longer if the medication has a long half life
• Excessive intake of caffeine-containing drinks or food (eg, coffee, tea, chocolate) as judged by the Investigator
• Inability to swallow acalabrutinib tablets or acalabrutinib capsules
• Evidence of ongoing systemic bacterial, fungal, or viral infection (including upper respiratory tract infections)

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (3)

Research Site

Glendale, California, 91206, United States

Location

Research Site

Brooklyn, Maryland, 21225, United States

Location

Research Site

Salt Lake City, Utah, 84107, United States

Location

Related Links

• Results of this clinical trial are available on www.astrazenecaclinicaltrials.com

MeSH Terms

Interventions

acalabrutinib

Study Officials

• Ronald Goldwater, MD

  Parexel Early Phase Clinical Unit Baltimore Harbor Hospital 3001 South Hanover St. Baltimore, MD 21225 USA

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: February 22, 2021
• First Posted: February 24, 2021
• Study Start: February 25, 2021
• Primary Completion: May 10, 2021
• Study Completion: May 10, 2021
• Last Updated: July 8, 2022

Record last verified: 2022-03

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 de-identified 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 (3)