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

Sponsor
Acerta Pharma BV (Industry)
Overall Status
Completed
CT.gov ID
NCT04898101
Collaborator
(none)
14
Enrollment
1
Location
2
Arms
1.3
Actual Duration (Months)
10.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed 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.

Study Design

Study Type:
Interventional
Actual Enrollment :
14 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Absolute Bioavailability, Pharmacokinetics, Excretion, and Metabolism of [14C]Acp-196 (Acalabrutinib) in Healthy Subjects
Actual Study Start Date :
Mar 3, 2016
Actual Primary Completion Date :
Apr 13, 2016
Actual Study Completion Date :
Apr 13, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cohort 1

Participants will receive a single 100 mg oral capsule dose of acalabrutinib and at 58 minutes postdose, participants will receive a single microtracer (<10 μg; <=1 μCi) [14C]ACP-196 as a 5 mL IV push over 2 minutes.

Drug: Acalabrutinib
Participants in Cohort 1 will receive a single 100 mg oral capsule dose of acalabrutinib on Day 1.
Other Names:
  • ACP-196

    • Drug: 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.
    Experimental: Cohort 2

    Participants 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.

    Drug: 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.

    Outcome Measures

    Primary Outcome Measures

    1. 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]

    2. 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]

    3. 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]

    4. 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]

    5. 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]

    6. 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]

    7. 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]

    8. 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]

    9. 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]

    10. 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]

    11. Apparent Terminal Elimination Rate Constant (λz) 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]

    12. 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]

    13. 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]

    14. 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]

    15. 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]

    16. 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]

    17. 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]

    18. 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]

    19. Ratio of Whole Blood to Plasma AUC0-∞ 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]

    20. 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]

    21. 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]

    22. 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]

    23. 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]

    24. 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 Outcome Measures

    1. 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]

    2. 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]

    3. 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]

    4. Incidence of Abnormal ECGs Reported as TEAEs [Cohort 1: From Day 1 through Day 5; Cohort 2: From Day 1 through Day 8]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Covance Clinical Research Unit, Inc. Madison Wisconsin United States 53704

    Sponsors and Collaborators

    • Acerta Pharma BV

    Investigators

    • Study Director: Priti Patel, Acerta Pharma BV

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Acerta Pharma BV
    ClinicalTrials.gov Identifier:
    NCT04898101
    Other Study ID Numbers:
    • ACE-HV-009
    First Posted:
    May 24, 2021
    Last Update Posted:
    May 24, 2021
    Last Verified:
    May 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Acerta Pharma BV
    ACP-196
    Acalabrutinib
    [14C]Acp-196
    Healthy participants
    Volunteers
    Adults
    Pharmacokinetics
    PK
    Bioavailability
    Excretion
    Metabolism
    Additional relevant MeSH terms:
    Acalabrutinib

    Study Results

    No Results Posted as of May 24, 2021