A Study to Evaluate the Effect of Gastric pH on Acalabrutinib Pharmacokinetics (PK) in Healthy Adult Participants
- Registration Number
- NCT04905043
- Lead Sponsor
- Acerta Pharma BV
- Brief Summary
This study will evaluate the effect of gastric pH on acalabrutinib pharmacokinetics in healthy participants.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 12
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description SmartPill® + Acalabrutinib SmartPill® 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. SmartPill® + Acalabrutinib 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.
- Primary Outcome Measures
Name Time Method 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 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 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 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
Name Time Method 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 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 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 Electrocardiograms (ECGs) Reported as TEAEs Day 1 to Day 5 for each participant 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 Incidences of Abnormal Vital Signs and Physical Examinations 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
Trial Locations
- Locations (1)
Celerion
🇺🇸Tempe, Arizona, United States