A Study to Evaluate the Effect of Gastric pH on Acalabrutinib Pharmacokinetics (PK) in Healthy Adult Participants

A Phase 1, Single-center, Open-label, Fixed-sequence, 2-period Study in Healthy Adult Subjects to Evaluate the Effect of Gastric pH on Acalabrutinib Pharmacokinetics

This study will evaluate the effect of gastric pH on acalabrutinib pharmacokinetics in healthy participants.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: Acalabrutinib; Drug: SmartPill®

Detailed Description

This is a 2-period study done under fasting conditions. Participants will receive an oral wireless motility/pH capsule (SmartPill®) followed immediately by a single 100 mg oral dose of acalabrutinib on Day 1 of Period 1 and Period 2 (ie, Day 1 and Day 4, respectively). There will be 72 hours of washout between Day 1 dosing of each period. Participants will be contacted approximately 14 days after the last dose of study drug for adverse events.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

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

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 nonsmoker 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.
• Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or ECGs, as deemed by the principal investigator. Liver function tests, and serum bilirubin, must be <= upper limit of normal range (ULN) at screening.
• Minimum of 1 bowel movement per day for >= 3 months before enrollment.
• 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.

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.
• Participant has any of the following contraindications for the SmartPill: A history of gastric bezoars, swallowing disorder, suspected or known strictures, fistulas or physiological/mechanical gastrointestinal (GI) obstruction, history of GI surgery within 3 months of administration, severe dysphagia to food or pills, Crohn's disease or diverticulitis, cardiac pacemakers or other implanted electromedical devices.
• History or presence of alcoholism or drug abuse within the past 2 years before screening
• History of bleeding diathesis
• History of gastric motility disorder for example delayed gastric emptying, dumping syndrome, or irritable bowel disease.
• History of constipation within the last year before enrollment
• Currently experiencing, or experienced within 2 weeks of enrollment, Grade 2 diarrhea
• 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 mmHg or > 140/90 mmHg at screening.
• Seated heart rate is lower than 40 bpm or higher than 99 bpm at screening.
• Have been on a diet incompatible with the on study diet, in the opinion of the principal investigator (PI), within the 28 days before the first dose of study drug, and throughout the study.
• Unable to refrain from or anticipates the use of protocol defined medications.
• History or presence of liver disease and clostridium difficile-associated diarrhea.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SmartPill® + Acalabrutinib; Participants will receive 1 SmartPill® capsule followed immediately by a single oral dose of acalabrutinib 100 mg capsule on Day 1 (Period 1) and Day 4 (Period 2). There will be 72 hours of washout between acalabrutinib dosing of each period.	Drug: Acalabrutinib; Participants will receive a single oral dose of acalabrutinib 100 mg capsule on Day 1 (Period 1) and Day 4 (Period 2).; Other Names: ACP-196; Drug: SmartPill®; Participnats will receive a single oral dose of wireless motility/pH capsule (SmartPill®) on Day 1 (Period 1) and Day 4 (Period 2).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Effect of Gastric pH and Emptying Rate on Acalabrutinib PK Parameters (Area Under Concentration-time Curve [AUC] From Time 0 to Last Measurable Concentration, AUC From Time 0 to Infinity, Maximum Observed Plasma Concentration [Cmax], Time to Reach Cmax)	0, 3, 8, and 17 minutes post-ingestion event time (IET) in Periods 1 and 2
Area Under the Plasma Concentration-time Curve From Time 0 to Time of Last Measurable Concentration (AUC0-last) of Acalabrutinib	pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose in Periods 1 and 2
Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of Acalabrutinib	pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose in Periods 1 and 2
Maximum Observed Plasma Concentration (Cmax) of Acalabrutinib	pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose in Periods 1 and 2

Secondary Outcome Measures

Outcome Measure	Time Frame
Percent of AUC0-inf Extrapolated (AUC%extrap) of Acalabrutinib	pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose in Periods 1 and 2
Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours (AUC0-6h) of Acalabrutinib	pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose in Periods 1 and 2
Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours (AUC0-12h) of Acalabrutinib	pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose in Periods 1 and 2
Time to Reach Maximum Observed Plasma Concentration (Tmax) of Acalabrutinib	pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose in Periods 1 and 2
Apparent Terminal Elimination Rate Constant (λz) of Acalabrutinib	pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose in Periods 1 and 2
Apparent Terminal Elimination Half-life (T1/2) of Acalabrutinib	pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose in Periods 1 and 2
Apparent Total Plasma Clearance (CL/F) of Acalabrutinib	pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose in Periods 1 and 2
Apparent Volume of Distribution (Vz/F) of Acalabrutinib	pre-dose; and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, and 24 hours post-dose in Periods 1 and 2
Incidences of Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	Day 1 through 14 days after the last dose (approximately 1 month)
Incidences of Abnormal Vital Signs and Physical Examinations Reported as TEAEs	Day 1 to Day 5 for each participant
Incidences of Abnormal Electrocardiograms (ECGs) Reported as TEAEs	Day 1 to Day 5 for each participant
Incidences of Abnormal Clinical Laboratory Parameters Reported as TEAEs	Day 1 to Day 5 for each participant

Collaborators and Investigators

• Sponsor: Acerta Pharma BV

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2016
• Primary Completion (Actual): July 11, 2016
• Study Completion (Actual): July 11, 2016

Study Registration Dates

• First Submitted: May 24, 2021
• First Submitted That Met QC Criteria: May 24, 2021
• First Posted (Actual): May 27, 2021

Study Record Updates

• Last Update Posted (Actual): June 3, 2021
• Last Update Submitted That Met QC Criteria: June 2, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Keywords: Safety; Pharmacokinetics; PK; Healthy participants; Gastric pH; Acalabrutinib; ACP-196
• Additional Relevant MeSH Terms: Antineoplastic Agents; Acalabrutinib
• Other Study ID Numbers: ACE-HV-113

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 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