Clinical trial NCT04905043: A Study to Evaluate the Effect of Gastric pH on Acalabrutinib Pharmacokinetics (PK) in Healthy Adult Participants
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Keywords: Acalabrutinib
ACP-196
Gastric pH
Healthy participants
Pharmacokinetics
PK
Safety
Lead sponsor: Acerta Pharma BV
Sponsor class: INDUSTRY
First posted: 2021-05-27
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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)
timeFrame: 0, 3, 8, and 17 minutes post-ingestion event time (IET) in Periods 1 and 2
measure: Area Under the Plasma Concentration-time Curve From Time 0 to Time of Last Measurable Concentration (AUC0-last) of Acalabrutinib
timeFrame: 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
measure: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of Acalabrutinib
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) of Acalabrutinib
timeFrame: 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:
measure: Percent of AUC0-inf Extrapolated (AUC%extrap) of Acalabrutinib
timeFrame: 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
measure: Area Under the Plasma Concentration-time Curve From Time 0 to 6 Hours (AUC0-6h) of Acalabrutinib
timeFrame: 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
measure: Area Under the Plasma Concentration-time Curve From Time 0 to 12 Hours (AUC0-12h) of Acalabrutinib
timeFrame: 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
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Acalabrutinib
timeFrame: 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
measure: Apparent Terminal Elimination Rate Constant (λz) of Acalabrutinib
timeFrame: 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
measure: Apparent Terminal Elimination Half-life (T1/2) of Acalabrutinib
timeFrame: 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
measure: Apparent Total Plasma Clearance (CL/F) of Acalabrutinib
timeFrame: 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
measure: Apparent Volume of Distribution (Vz/F) of Acalabrutinib
timeFrame: 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
measure: Incidences of Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
timeFrame: Day 1 through 14 days after the last dose (approximately 1 month)
measure: Incidences of Abnormal Vital Signs and Physical Examinations Reported as TEAEs
timeFrame: Day 1 to Day 5 for each participant
measure: Incidences of Abnormal Electrocardiograms (ECGs) Reported as TEAEs
timeFrame: Day 1 to Day 5 for each participant
measure: Incidences of Abnormal Clinical Laboratory Parameters Reported as TEAEs
timeFrame: Day 1 to Day 5 for each participant
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Celerion
state: Arizona
Study officials:
References: