Healthy Volunteers
Conditions
Keywords
Acalabrutinib, ACP-196, Gastric pH, Healthy participants, Pharmacokinetics, PK, Safety
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.
Interventions
DRUGAcalabrutinib
Participants will receive a single oral dose of acalabrutinib 100 mg capsule on Day 1 (Period 1) and Day 4 (Period 2).
DRUGSmartPill®
Participnats will receive a single oral dose of wireless motility/pH capsule (SmartPill®) on Day 1 (Period 1) and Day 4 (Period 2).
Sponsors
Acerta Pharma BV
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| 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 |
| 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) |
| 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 |
Countries
United States
Outcome results
None listed