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

NCT04905043 | Completed Phase 1 FDA Drug

• 1 other identifier: ACE-HV-113
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Healthy Volunteers

Keywords

Acalabrutinib; ACP-196; Gastric pH; Healthy participants; Pharmacokinetics; PK; Safety

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (12)

• 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

Study Arms (1)

SmartPill® + Acalabrutinib

EXPERIMENTAL

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; Drug: SmartPill®

Interventions

Acalabrutinib DRUG

Participants will receive a single oral dose of acalabrutinib 100 mg capsule on Day 1 (Period 1) and Day 4 (Period 2).

Also known as: ACP-196

SmartPill® + Acalabrutinib

SmartPill® DRUG

Participnats will receive a single oral dose of wireless motility/pH capsule (SmartPill®) on Day 1 (Period 1) and Day 4 (Period 2).

SmartPill® + Acalabrutinib

Eligibility Criteria

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

You may qualify if:

• 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.

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 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.

Sponsors & Collaborators

• Acerta Pharma BV: lead

Study Sites (1)

Celerion

Tempe, Arizona, 85283, United States

Location

MeSH Terms

Interventions

acalabrutinib

Study Design

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

Study Record Dates

• First Submitted: May 24, 2021
• First Posted: May 27, 2021
• Study Start: June 3, 2016
• Primary Completion: July 11, 2016
• Study Completion: July 11, 2016
• Last Updated: June 3, 2021

Record last verified: 2021-06

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)