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

Healthy Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04905043
• Other study ID #: ACE-HV-113
• Status: Completed
• Phase: Phase 1
• Start date: June 3, 2016
• Est. completion date: July 11, 2016

Study information

• Verified date: June 2021
• Source: Acerta Pharma BV
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: July 11, 2016
• Est. primary completion date: July 11, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Acalabrutinib
Participants will receive a single oral dose of acalabrutinib 100 mg capsule on Day 1 (Period 1) and Day 4 (Period 2).
• SmartPill®
Participnats will receive a single oral dose of wireless motility/pH capsule (SmartPill®) on Day 1 (Period 1) and Day 4 (Period 2).

Locations

Country	Name	City	State
United States	Celerion	Tempe	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Acerta Pharma BV

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Apparent Terminal Elimination Rate Constant (?z) 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	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	Incidences of Abnormal Vital Signs and Physical Examinations Reported as TEAEs		Day 1 to Day 5 for each participant
Secondary	Incidences of Abnormal Electrocardiograms (ECGs) Reported as TEAEs		Day 1 to Day 5 for each participant
Secondary	Incidences of Abnormal Clinical Laboratory Parameters Reported as TEAEs		Day 1 to Day 5 for each participant