A Study to Evaluate the Effect of [14C]Acp-196 (Acalabrutinib) in Healthy Adult Participants

Healthy Volunteers Clinical Trial

Official title:

Absolute Bioavailability, Pharmacokinetics, Excretion, and Metabolism of [14C]Acp-196 (Acalabrutinib) in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04898101
• Other study ID #: ACE-HV-009
• Status: Completed
• Phase: Phase 1
• Start date: March 3, 2016
• Est. completion date: April 13, 2016

Study information

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

Clinical Trial Summary

This study is to determine the absolute bioavailability of oral acalabrutinib and intravenous (IV) PK of [14C]ACP-196.

Description:

This is 2-cohort study. Screening period will be within 28 days before the dose. In the treatment period, participants in Cohort 1 will receive a single 100 mg oral capsule dose of acalabrutinib and at 58 minutes postdose of acalabrutinib will receive a single microtracer (<10 μg; <=1 μCi) [14C]ACP-196 as a 5 mL IV push over 2 minutes; and participants in Cohort 2 will receive a single 100 mL oral solution of acalabrutinib (1 mg/mL oral solution containing a microtracer dose (<10 μg; <=1 μCi) of [14C]ACP-196). Cohort 1 participants will be confined continuously from Check-in until Day 5 and Cohort 2 participants will be confined continuously from Check-in until Day 8.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 14
• Est. completion date: April 13, 2016
• Est. primary completion date: April 13, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Continuous non-smoker who has not used nicotine-containing products within 3 months before Check-in and during the entire study

• Body mass index (BMI) >= 18.5 to <= 29.9 kg/m^2 at Screening

• Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or electrocardiograms (ECGs), as deemed by the investigator

• Women must be of non-childbearing status and have negative serum pregnancy test results at Screening and Check-in

• Male participants must be willing to use protocol specified contraception methods

• A minimum of 1 bowel movement per day (Cohort 2 only)

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

• History of any illness that, in the opinion of the investigator, might confound the results of the study or poses an additional risk to the participant by their participation in the study

• Presence of any clinically significant, ongoing systemic bacterial, fungal, or viral infections in the opinion of the investigator

• History or presence of alcoholism or drug abuse within the past 2 years before Screening

• History of bleeding diathesis

• Any clinically significant condition that may affect acalabrutinib absorption in the opinion of the investigator, including gastric restrictions and bariatric surgery (eg, gastric bypass)

• History or presence of clinically significant thyroid disease, in the opinion of the investigator

• Women who are pregnant, breastfeeding, or lactating

• Positive test for selected drugs of abuse at Screening and at Check-in

• Known history of human immunodeficiency virus (HIV), serologic status reflecting active or past history of hepatitis B or C infection, or any uncontrolled active systemic infection

• Supine blood pressure is < 90/40 mmHg or > 140/90 mmHg at Screening

• Supine pulse is < 40 beats per minute or > 99 beats per minute at Screening

• Have been on a diet incompatible with the on-study diet, in the opinion of the Investigator, within the 28 days before the dose of study drug, and throughout the study

• Unable to refrain from or anticipates the use of any drugs, including prescription and non-prescription medications

• Participation in more than 1 other radiolabeled investigational study drug trial within 12 months before Check-in

• Exposure to significant radiation (eg, serial x-ray or computed tomography scans, barium meal) or current employment in a job requiring radiation exposure monitoring, with either being within 12 months before Check-in

• Poor peripheral venous access

• Unwilling to consume trace amounts of ethanol (alcohol) that may be present in the dose formulation

• History or presence of liver disease or cholecystectomy and Clostridium difficile associated diarrhea

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Acalabrutinib
Participants in Cohort 1 will receive a single 100 mg oral capsule dose of acalabrutinib on Day 1.
• Microtracer [14C]ACP-196
Participants in Cohort 1 will receive a single microtracer (<10 µg; =1 µCi) IV solution dose of [14C]ACP-196 as a 5-mL IV push over 2 minutes on Day 1. Participants in Cohort 2 will receive a single 100 mL dose of acalabrutinib 1 mg/mL oral solution containing a microtracer dose (<10 µg; =1 µCi) of [14C]ACP-196 on Day 1.

Locations

Country	Name	City	State
United States	Covance Clinical Research Unit, Inc.	Madison	Wisconsin

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	Absolute bioavailability (F) of Acalabrutinib for Cohort 1		Cohort 1: 0, 15, 30, 45, 58 min; post IV at 0, 5, 10, 15, 20, 30 min; and post oral dose at 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, 72, 96 hrs
Primary	Area Under the Concentration-time Curve From Hour 0 to the Last Quantifiable Concentration (AUC0-t) of Acalabrutinib and [14C]ACP-196 for Cohort 1 and Cohort 2		Cohort 1: 0, 15, 30, 45, 58min; post IV at 0, 5, 10, 15, 20, 30min; and post oral dose at 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, 72, 96hrs; Cohort 2: 0, 15, 30, 45, 60, 75, 90min, and at 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168hrs postdose
Primary	Area Under the Concentration-time Curve From Hour 0 to Hour 12 (AUC0-12h) of Acalabrutinib and [14C]ACP-196 for Cohort 1 and Cohort 2		Cohort 1: 0, 15, 30, 45, 58min; post IV at 0, 5, 10, 15, 20, 30min; and post oral dose at 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, 72, 96hrs; Cohort 2: 0, 15, 30, 45, 60, 75, 90min, and at 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168hrs postdose
Primary	Area Under the Concentration-time Curve From Hour 0 to Hour 72 (AUC0-72h) of Acalabrutinib and [14C]ACP-196 for Cohort 1		Cohort 1: 0, 15, 30, 45, 58 min; post IV at 0, 5, 10, 15, 20, 30 min; and post oral dose at 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, 72, 96 hrs
Primary	Area Under the Concentration-time Curve From Hour 0 to Hour 168 (AUC0-168h) of Acalabrutinib and [14C]ACP-196 for Cohort 2		Cohort 2: 0, 15, 30, 45, 60, 75, 90 min, and at 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hrs postdose
Primary	Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of Acalabrutinib and [14C]ACP-196 for Cohort 1 and Cohort 2		Cohort 1: 0, 15, 30, 45, 58min; post IV at 0, 5, 10, 15, 20, 30min; and post oral dose at 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, 72, 96hrs; Cohort 2: 0, 15, 30, 45, 60, 75, 90min, and at 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168hrs postdose
Primary	Percent of AUC0-inf Extrapolated (AUC%extrap) of ACP-196 for Cohort 1 and Cohort 2		Cohort 1: 0, 15, 30, 45, 58min; post IV at 0, 5, 10, 15, 20, 30min; and post oral dose at 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, 72, 96hrs; Cohort 2: 0, 15, 30, 45, 60, 75, 90min, and at 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168hrs postdose
Primary	Maximum Observed Concentration (Cmax) of Acalabrutinib and [14C]ACP-196 for Cohort 1 and Cohort 2		Cohort 1: 0, 15, 30, 45, 58min; post IV at 0, 5, 10, 15, 20, 30min; and post oral dose at 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, 72, 96hrs; Cohort 2: 0, 15, 30, 45, 60, 75, 90min, and at 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168hrs postdose
Primary	Time to Maximum Observed Concentration (tmax) of Acalabrutinib and [14C]ACP-196 for Cohort 1 and Cohort 2		Cohort 1: 0, 15, 30, 45, 58min; post IV at 0, 5, 10, 15, 20, 30min; and post oral dose at 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, 72, 96hrs; Cohort 2: 0, 15, 30, 45, 60, 75, 90min, and at 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168hrs postdose
Primary	Apparent Terminal Elimination Half-life (t1/2) of Acalabrutinib and [14C]ACP-196 for Cohort 1 and Cohort 2		Cohort 1: 0, 15, 30, 45, 58min; post IV at 0, 5, 10, 15, 20, 30min; and post oral dose at 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, 72, 96hrs; Cohort 2: 0, 15, 30, 45, 60, 75, 90min, and at 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168hrs postdose
Primary	Apparent Terminal Elimination Rate Constant (?z) of Acalabrutinib and [14C]ACP-196 for Cohort 1 and Cohort 2		Cohort 1: 0, 15, 30, 45, 58min; post IV at 0, 5, 10, 15, 20, 30min; and post oral dose at 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, 72, 96hrs; Cohort 2: 0, 15, 30, 45, 60, 75, 90min, and at 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168hrs postdose
Primary	Apparent Total Plasma Clearance (CL/F) of Acalabrutinib for Cohort 1 and Cohort 2		Cohort 1: 0, 15, 30, 45, 58min; post IV at 0, 5, 10, 15, 20, 30min; and post oral dose at 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, 72, 96hrs; Cohort 2: 0, 15, 30, 45, 60, 75, 90min, and at 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168hrs postdose
Primary	Total Plasma Clearance (CL) of [14C]ACP-196 for Cohort 1		Cohort 1: 0, 15, 30, 45, 58 min; post IV at 0, 5, 10, 15, 20, 30 min; and post oral dose at 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, 72, 96 hrs
Primary	Apparent Volume of Distribution During the Terminal Elimination Phase (Vz/F) of Acalabrutinib for Cohort 1 and Cohort 2		Cohort 1: 0, 15, 30, 45, 58min; post IV at 0, 5, 10, 15, 20, 30min; and post oral dose at 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, 72, 96hrs; Cohort 2: 0, 15, 30, 45, 60, 75, 90min, and at 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168hrs postdose
Primary	Volume of Distribution During the Terminal Phase (Vz) of [14C]ACP-196 for Cohort 1		Cohort 1: 0, 15, 30, 45, 58 min; post IV at 0, 5, 10, 15, 20, 30 min; and post oral dose at 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, 72, 96 hrs
Primary	Volume of Distribution at Steady State (Vss) of [14C]ACP-196 for Cohort 1		Cohort 1: 0, 15, 30, 45, 58 min; post IV at 0, 5, 10, 15, 20, 30 min; and post oral dose at 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, 72, 96 hrs
Primary	Mean Residence Time (MRT) of [14C]ACP-196 for Cohort 1		Cohort 1: 0, 15, 30, 45, 58 min; post IV at 0, 5, 10, 15, 20, 30 min; and post oral dose at 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 60, 72, 96 hrs
Primary	ACP-196:total 14C AUC0-inf Ratio for Cohort 2		Cohort 2: 0, 15, 30, 45, 60, 75, 90 min, and at 2, 2.5, 3, 4, 5, 6, 8, 12, 24, 48, 72, 96, 120, 144, 168 hrs postdose
Primary	Ratio of Whole Blood to Plasma AUC0-8 for Total Radioactivity for Cohort 2		Urine: -12 to 0 (before dose within 20 minutes), 0 to 6 hrs, 6 to 12 hrs, 12 to 24 hrs, and 24-hr intervals through 168 hrs postdose; Feces: predose (within 24 hours of dosing), 0 to 24 hrs postdose, and 24-hr intervals through 168 hrs postdose
Primary	Cumulative Amount of Drug Excreted in Urine (Aeu) of Acalabrutinib and [14C]ACP-196 for Cohort 1		Urine at -12 to 0 (before dose, up to the last void within 20 minutes before oral dosing), 0 to 6 hrs, 6 to 12 hrs, 12 to 24hrs, 24 to 48hrs, and 48 to 72hrs post oral dose
Primary	Renal Clearance (CLR) of Acalabrutinib and [14C]ACP-196 for Cohort 1		Urine at -12 to 0 (before dose, up to the last void within 20 minutes before oral dosing), 0 to 6 hrs, 6 to 12 hrs, 12 to 24hrs, 24 to 48hrs, and 48 to 72hrs post oral dose
Primary	Cumulative Percent of Dose Excreted in Urine (%feu) of Acalabrutinib and [14C]ACP-196 for Cohort 1		Urine at -12 to 0 (before dose, up to the last void within 20 minutes before oral dosing), 0 to 6 hrs, 6 to 12 hrs, 12 to 24hrs, 24 to 48hrs, and 48 to 72hrs post oral dose
Primary	Cumulative Amount of Drug Excreted in Urine of Acalabrutinib and Urine and Fecal (Ae) of [14C]ACP-196 for Cohort 2		Urine: -12 to 0 (before dose within 20 minutes), 0 to 6 hrs, 6 to 12 hrs, 12 to 24 hrs, and 24-hr intervals through 168 hrs postdose; Feces: predose (within 24 hours of dosing), 0 to 24 hrs postdose, and 24-hr intervals through 168 hrs postdose
Primary	Cumulative Percent of Dose Excreted in Urine of Acalabrutinib and Urine and Fecal (%fe) of [14C]ACP-196 for Cohort 2		Urine: -12 to 0 (before dose within 20 minutes), 0 to 6 hrs, 6 to 12 hrs, 12 to 24 hrs, and 24-hr intervals through 168 hrs postdose; Feces: predose (within 24 hours of dosing), 0 to 24 hrs postdose, and 24-hr intervals through 168 hrs postdose
Secondary	Incidence of Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)		Cohort 1: From Day 1 through Day 5; Cohort 2: From Day 1 through Day 8
Secondary	Incidence of Abnormal Clinical Laboratory Parameters Reported as TEAEs		Cohort 1: From Day 1 through Day 5; Cohort 2: From Day 1 through Day 8
Secondary	Incidence of Abnormal Vital Signs and Physical Examinations Reported as TEAEs		Cohort 1: From Day 1 through Day 5; Cohort 2: From Day 1 through Day 8
Secondary	Incidence of Abnormal ECGs Reported as TEAEs		Cohort 1: From Day 1 through Day 5; Cohort 2: From Day 1 through Day 8