A Study of Acalabrutinib Suspension to Evaluate Relative Bioavailability and Proton-pump Inhibitor Effect in Healthy Volunteers

NCT04435483 | Completed Phase 1 FDA Drug

• 1 other identifier: D822FC00004
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being conducted to support the clinical development of acalabrutinib in patients who are unable to swallow capsule and require nasogastric (NG) tube placement.

Conditions

Pharmacokinetics; Bioavailability

Keywords

Calquence; Acalabrutinib

Outcome Measures

Primary Outcomes (3)

• Acalabrutinib and ACP-5862 plasma PK parameter: Area under plasma concentration-time curve from time zero to infinity (AUCinf)

  To compare the AUCinf of the acala NG suspension with and without rabeprazole. To compare the AUC of the acala NG suspension with the oral capsule.

  Day 1 to 2: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 hours (h) post-dose

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

  To compare the AUClast of the acala NG suspension with and without rabeprazole. To compare the AUClast of the acala NG suspension with the oral capsule.

  Day 1 to 2: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 h post-dose

• Acalabrutinib and ACP-5862 plasma PK parameter: Maximum observed plasma concentration (Cmax)

  To compare the Cmax of the acala NG suspension with and without rabeprazole. To compare the Cmax of the acala NG suspension with the oral capsule.

  Day 1 to 2: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 h post-dose

Secondary Outcomes (12)

• Acalabrutinib and ACP-5862 plasma PK parameter: Area under the plasma concentration-time curve from time zero to 24 hours post-dose (AUC0-24)

  Day 1 to 2: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 h post-dose

• Acalabrutinib and ACP-5862 plasma PK parameter: Time to reach maximum observed plasma concentration (tmax)

  Day 1 to 2: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 h post-dose

• Acalabrutinib and ACP-5862 plasma PK parameter: Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t1/2)

  Day 1 to 2: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 h post-dose

• Acalabrutinib and ACP-5862 plasma PK parameter: Mean residence time of the drug in the systemic circulation from zero to infinity (MRT)

  Day 1 to 2: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 h post-dose

• Acalabrutinib and ACP-5862 plasma PK parameter: Terminal elimination rate constant (λz)

  Day 1 to 2: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24 h post-dose

Study Arms (2)

Treatment Sequence 1

EXPERIMENTAL

Participants will receive Treatment A (100 mg acalabrutinib suspension via NG administration plus 20 mg rabeprazole) in Period 1, Treatment B (100 mg acalabrutinib suspension via NG administration) in Period 2, and Treatment C (100 mg acalabrutinib capsule) in Period 3.

Drug: Acalabrutinib Treatment A; Drug: Acalabrutinib Treatment B; Drug: Acalabrutinib Treatment C

Treatment Sequence 2

EXPERIMENTAL

Participants will receive Treatment B (100 mg acalabrutinib suspension via NG administration) in Period 1, Treatment C (100 mg acalabrutinib capsule) in Period 2, and Treatment B (100 mg acalabrutinib suspension via NG administration) in Period 3.

Drug: Acalabrutinib Treatment B; Drug: Acalabrutinib Treatment C

Interventions

Acalabrutinib Treatment A DRUG

Participants will receive a single dose of 100-mg acalabrutinib suspension via NG administration, under fasted conditions. A single dose of 20 mg rabeprazole will be administered with 240 mL water, 2 hours prior to administration of acalabrutinib suspension. Treatment with rabeprazole 20 mg twice daily (with meals) will be started 3 days prior to the receiving the first dose of acalabrutinib suspension.

Treatment Sequence 1

Acalabrutinib Treatment B DRUG

Participants will receive a single dose of 100-mg acalabrutinib suspension via NG administration, under fasted conditions.

Treatment Sequence 1; Treatment Sequence 2

Acalabrutinib Treatment C DRUG

Participants will receive a single dose of 100-mg acalabrutinib capsule, under fasted conditions. The acalabrutinib capsule will be administered with 240 mL of water.

Treatment Sequence 1; Treatment Sequence 2

Eligibility Criteria

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

You may qualify if:

• Provision of signed and dated, written informed consent prior to any study-specific procedures.
• Healthy adult male and female subjects aged 18 to 55 years (inclusive) with suitable veins for cannulation or repeated venipuncture.
• Male subjects and their female partners/spouses must adhere to the contraception methods.
• Female subjects must have a negative pregnancy test at screening, must not be lactating, and must be of non-childbearing potential.
• Have a body mass index (BMI) between 18.5 and 30 kg/m2, inclusive, and weigh at least 50 kg and no more than 100 kg, inclusive, at screening.

You may not qualify if:

• History or presence of any clinically significant disease (including COVID-19) or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
• History or presence of gastrointestinal (GI), hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• Any positive result on screening for serum hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
• Plasma donation within 30 days of screening or any blood donation/loss more than 500 mL during the 90 days prior to screening.
• Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the 90 days prior to screening.
• Positive screen for drugs of abuse or cotinine at screening.
• Known or suspected history of alcohol or drug abuse, or excessive intake of alcohol as judged by the Investigator.
• Excessive intake of caffeine-containing drinks or food as judged by the Investigator.
• Vulnerable subjects, eg, kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
• History of a disorder which would make NG tube placement contraindicated, eg, esophageal strictures, esophageal varices, or bleeding diathesis.
• Evidence of ongoing systemic bacterial, fungal, or viral infection (including upper respiratory tract infections). Subjects with localized cutaneous fungal infections are eligible.

Sponsors & Collaborators

• AstraZeneca: lead
• Acerta Pharma, LLC: collaborator

Study Sites (1)

Research Site

Glendale, California, 91206, United States

Location

Study Officials

• David Han, M.D.

  PAREXEL Early Phase Clinical Unit-Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: June 1, 2020
• First Posted: June 17, 2020
• Study Start: May 22, 2020
• Primary Completion: June 26, 2020
• Study Completion: June 26, 2020
• Last Updated: July 22, 2020

Record last verified: 2020-07

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 (1)