A Study to Evaluate the Effect of Pharmacokinetics (PK) of Acalabrutinib and Its Active Metabolite (ACP-5862) When Administered Alone and With Moderate CYP3A4 Inhibitors Fluconazole or Isavuconazole in Healthy Adult Participants

NCT05140096 | Completed Phase 1 FDA Drug

• 1 other identifier: ACE-HV-114
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the effect of fluconazole and isavuconazole on the PK of acalabrutinib and its active metabolite, ACP-5862.

Conditions

Healthy Volunteers

Keywords

Healthy participants; Acalabrutinib; ACP-196, Active metabolite; ACP-5862; Fluconazole; Isavuconazole; CYP3A4 Inhibitors; Pharmacokinetics; PK; Safety

Outcome Measures

Primary Outcomes (3)

• Area Under the Plasma Concentration-time Curve to the Last Observed Nonzero Concentration (AUC0-t) of Acalabrutinib and ACP-5862

  Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-acalabrutinib dose in each period (i.e., Days 1 to 2 for Treatments A and B and Days 5 to 6 for Treatment C)

• Area Under the Plasma Concentration-time Curve to Infinity (AUC0-inf) of Acalabrutinib and ACP-5862

  Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-acalabrutinib dose in each period (i.e., Days 1 to 2 for Treatments A and B and Days 5 to 6 for Treatment C)

• Maximum Observed Plasma Concentration (Cmax) of Acalabrutinib and ACP-5862

  Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-acalabrutinib dose in each period (i.e., Days 1 to 2 for Treatments A and B and Days 5 to 6 for Treatment C)

Secondary Outcomes (14)

• Percent of Area Under the Plasma Concentration-time Curve to Infinity Extrapolated (AUC%extrap) of Acalabrutinib and ACP-5862

  Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-acalabrutinib dose in each period (i.e., Days 1 to 2 for Treatments A and B and Days 5 to 6 for Treatment C)

• Time of the Maximum Observed Plasma Concentration (Tmax) of Acalabrutinib and ACP-5862

  Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-acalabrutinib dose in each period (i.e., Days 1 to 2 for Treatments A and B and Days 5 to 6 for Treatment C)

• Time of the Last Measurable Nonzero Plasma Concentration (Tlast) of Acalabrutinib and ACP-5862

  Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-acalabrutinib dose in each period (i.e., Days 1 to 2 for Treatments A and B and Days 5 to 6 for Treatment C)

• Apparent Terminal Elimination Half-life (T1/2) of Acalabrutinib and ACP-5862

  Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-acalabrutinib dose in each period (i.e., Days 1 to 2 for Treatments A and B and Days 5 to 6 for Treatment C)

• Apparent Terminal Elimination Rate Constant (Kel) of Acalabrutinib and ACP-5862

  Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-acalabrutinib dose in each period (i.e., Days 1 to 2 for Treatments A and B and Days 5 to 6 for Treatment C)

Study Arms (2)

Treatment AB

EXPERIMENTAL

Participants will receive a single oral dose 100 mg acalabrutinib capsule on Day 1 of Period 1 (Treatment A) and later will receive single oral loading dose of 400 mg fluconazole tablets on Day 1, one hour prior to a single oral dose of 100 mg acalabrutinib in Period 2 (Treatment B).

Drug: Acalabrutinib; Drug: Fluconazole

Treatment AC

EXPERIMENTAL

Participants will receive a single oral dose 100 mg acalabrutinib capsule on Day 1 of Period 1 (Treatment A), and later will receive oral dose of 200 mg iscavuconazole capsules three times daily (approximately every 8 hours apart) on Day 1, followed by 200 mg iscavuconazole capsule once daily from Day 2 to Day 5 with a single oral dose of 100 mg acalabrutinib capsule coadministered on Day 5 in Period 2 (Treatment C).

Drug: Acalabrutinib; Drug: Isavuconazole

Interventions

Acalabrutinib DRUG

Modify as "Participants will receive a single oral dose of 100 mg (1 X 100 mg capsule) acalabrutinib either on Day 1 of Period 1 (Treatment A) and Day 1 of Period 2 (Treatment B) or Day 5 of Period 2 (Treatment C).

Treatment AB; Treatment AC

Fluconazole DRUG

Participants will receive 400 mg fluconazole (2 × 200 mg tablets) on Day 1 Period 2 (Treatment B).

Treatment AB

Isavuconazole DRUG

Participant will receive oral dose of 200 mg isavuconazole (2 × 186 mg of isavuconazonium sulfate capsules) three times daily on Day 1 and 200 mg isavuconazole (2 × 186 mg of isavuconazonium sulfate capsules) once daily on Days 2 to 5 in Period 2 (Treatment C).

Treatment AC

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Continuous non-smoker participant who has not used nicotine-containing products for at least 3 months prior to the first dosing and throughout the study
• Have body mass index of \>= 18 kg/m\^2 and \<= 32 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 (PI)
• Women participants must be of non-childbearing status and must have undergone the protocol specified sterilization procedures, and have official documentation, at least 6 months prior to the first dose; or be postmenopausal with amenorrhea for at least 1 year prior to the first dose and follicle-stimulating hormone serum levels consistent with postmenopausal status
• Male participants must be willing to use protocol specified contraception methods
• Male participants must agree not to donate sperm from the first dosing until 90 days after the last dosing
• Ability to swallow multiple capsules and/or tablets using size 0 blank capsules (up to a maximum of 3 capsules per participant)

You may not qualify if:

• 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 or presence of clinically significant medical or psychiatric condition or disease in the opinion of the PI or designee
• History of any illness that, in the opinion of the PI, 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 (including upper respiratory tract infections, but excluding localized cutaneous fungal infections), in the opinion of the PI
• History of any major surgical procedure within 30 days before the first dose of study drug
• History or presence of alcoholism or drug abuse within the past 2 years prior to the first dosing
• History or presence of clinically significant hypersensitivity or idiosyncratic reaction to acalabrutinib, fluconazole, isavuconazole, related compounds, or any inactive ingredients
• History or presence of liver disease and diabetes mellitus
• History of stroke or intracranial hemorrhage within 6 months before the first dosing
• History of bleeding diathesis
• Any clinically significant condition that may affect acalabrutinib absorption in the opinion of the PI, including gastric restrictions and bariatric surgery (eg, gastric bypass). Participants with cholecystectomy will be allowed.
• QTcF interval is \>460 msec (males) or \>470 msec (females) or has ECG findings deemed abnormal with clinical significance by the PI or designee at screening
• Women who are pregnant or lactating
• Positive urine drug or alcohol results at screening or first check-in
• Positive urine cotinine at screening

Sponsors & Collaborators

• Acerta Pharma BV: lead

Study Sites (1)

Celerion

Tempe, Arizona, 85283, United States

Location

MeSH Terms

Interventions

acalabrutinib; Fluconazole; isavuconazole

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2021
• First Posted: December 1, 2021
• Study Start: January 3, 2020
• Primary Completion: April 15, 2020
• Study Completion: April 15, 2020
• Last Updated: December 1, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

US (1)