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

Phase I, Open-label, Single-dose, Sequential, Randomized, Crossover Study of Acalabrutinib Suspension Delivered Via Nasogastric Tube in Healthy Subjects to Evaluate Relative Bioavailability and Proton-pump Inhibitor (Rabeprazole) Effect

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.

Study Overview

• Status: Completed
• Conditions: Pharmacokinetics; Bioavailability
• Intervention / Treatment: Drug: Acalabrutinib Treatment A; Drug: Acalabrutinib Treatment B; Drug: Acalabrutinib Treatment C

Detailed Description

This is an open-label, single-center, randomized, 3-period, crossover study of acalabrutinib suspension administered via NG tube in healthy subjects to evaluate the relative bioavailability and proton-pump inhibitor (rabeprazole) effect.

The study is divided in 3 periods.

Period 1 of the study is designed to investigate the effect of proton-pump inhibitor on the pharmacokinetics (PK) of acalabrutinib suspension. Period 2 and 3 of the study are designed to investigate the bioavailability of acalabrutinib suspension relative to an oral capsule formulation.

• Study Type: Interventional
• Enrollment (Actual): 39
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Provision of signed and dated, written informed consent prior to any study-specific procedures.
2. Healthy adult male and female subjects aged 18 to 55 years (inclusive) with suitable veins for cannulation or repeated venipuncture.
3. Male subjects and their female partners/spouses must adhere to the contraception methods.
4. Female subjects must have a negative pregnancy test at screening, must not be lactating, and must be of non-childbearing potential.
5. 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.

Exclusion Criteria:

1. 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.
2. 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.
3. Any positive result on screening for serum hepatitis B surface antigen, hepatitis B core antibody, hepatitis C antibody, and human immunodeficiency virus (HIV) antibody.
4. Plasma donation within 30 days of screening or any blood donation/loss more than 500 mL during the 90 days prior to screening.
5. Current smokers or those who have smoked or used nicotine products (including e-cigarettes) within the 90 days prior to screening.
6. Positive screen for drugs of abuse or cotinine at screening.
7. Known or suspected history of alcohol or drug abuse, or excessive intake of alcohol as judged by the Investigator.
8. Excessive intake of caffeine-containing drinks or food as judged by the Investigator.
9. Vulnerable subjects, eg, kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
10. History of a disorder which would make NG tube placement contraindicated, eg, esophageal strictures, esophageal varices, or bleeding diathesis.
11. Evidence of ongoing systemic bacterial, fungal, or viral infection (including upper respiratory tract infections). Subjects with localized cutaneous fungal infections are eligible.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Sequence 1; 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; 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.; Drug: Acalabrutinib Treatment B; Participants will receive a single dose of 100-mg acalabrutinib suspension via NG administration, under fasted conditions.; Drug: Acalabrutinib Treatment C; 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.
Experimental: Treatment Sequence 2; 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; Participants will receive a single dose of 100-mg acalabrutinib suspension via NG administration, under fasted conditions.; Drug: Acalabrutinib Treatment C; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acalabrutinib and ACP-5862 plasma PK parameter: Area under the plasma concentration-time curve from time zero to 24 hours post-dose (AUC0-24)	To compare the AUC0-24 of the acala NG suspension with and without rabeprazole. To compare the AUC0-24 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: Time to reach maximum observed plasma concentration (tmax)	To compare the tmax of the acala NG suspension with and without rabeprazole. To compare the tmax 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: Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t1/2)	To compare the t1/2 of the acala NG suspension with and without rabeprazole. To compare the t1/2 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: Mean residence time of the drug in the systemic circulation from zero to infinity (MRT)	To compare the MRT of the acala NG suspension with and without rabeprazole. To compare the MRT 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: Terminal elimination rate constant (λz)	To compare the λz of the acala NG suspension with and without rabeprazole. To compare the λz 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: Apparent total body clearance of drug from plasma after extravascular administration (acalabrutinib only) (CL/F)	To compare the CL/F of the acala NG suspension with and without rabeprazole. To compare the CL/F 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: Apparent volume of distribution during the terminal phase after extravascular administration (acalabrutinib only) (Vz/F)	To compare the Vz/F of the acala NG suspension with and without rabeprazole. To compare the Vz/F 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: Metabolite to parent ratio based on AUCinf and/or AUClast (M:P[AUC])	To compare the M:P[AUC] of the acala NG suspension with and without rabeprazole. To compare the M:P[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 h post-dose
Acalabrutinib and ACP-5862 plasma PK parameter: Metabolite to parent ratio based on Cmax (M:P[Cmax])	To compare the M:P[Cmax] of the acala NG suspension with and without rabeprazole. To compare the M:P[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
Number of subjects with abnormal vital signs	To assess the safety and tolerability of single doses of acalabrutinib suspension in healthy participants.	Screening, Day -1, and Day 2
Number of subjects with abnormal laboratory assessments	To assess the safety and tolerability of single doses of acalabrutinib suspension in healthy participants.	Screening, Day -1, Days 1-2, and follow-up visit (7-10 days after last dose)
Number of subjects with serious and non-serious adverse events	To assess the safety and tolerability of single doses of acalabrutinib suspension in healthy participants.	Screening (Day -28), Days -3, -2, -1, Days 1-3, and follow-up visit (7-10 days after last dose)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Acerta Pharma, LLC
• Investigators: Principal Investigator: David Han, M.D., PAREXEL Early Phase Clinical Unit-Los Angeles

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2020
• Primary Completion (Actual): June 26, 2020
• Study Completion (Actual): June 26, 2020

Study Registration Dates

• First Submitted: June 1, 2020
• First Submitted That Met QC Criteria: June 15, 2020
• First Posted (Actual): June 17, 2020

Study Record Updates

• Last Update Posted (Actual): July 22, 2020
• Last Update Submitted That Met QC Criteria: July 20, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Acalabrutinib; Calquence
• Additional Relevant MeSH Terms: Antineoplastic Agents; Acalabrutinib
• Other Study ID Numbers: D822FC00004

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

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 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

Drug and device information, study documents

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