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Healthy ParticipantsPhase 1NCT04901923

A Study to Evaluate Safety, Pharmacokinetics, Pharmacodynamics, Food Effects, and Drug-drug Interactions of ACP-196 in Healthy Participants

A Phase 1 study testing ACP-196 and Itraconazole in people with Healthy Participants, run by Acerta Pharma BV at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study is to evaluate the safety, pharmacokinetics/pharmacodynamics (PK/PD), food-effect, and drug-drug interaction study of ACP-196 in healthy participants. Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Healthy Participants
What is being tested?
ACP-196 and Itraconazole
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
59 participants
Where
1 siteUnited States
Study dates
15 Mar 2014to 22 May 2014
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Body mass index (BMI) >=18.0 and <=30.0 kg/m^2.
  • Healthy as determined by medical history and physical examination.
  • Nonsmoker
  • Normal clinical laboratory test results and ECG, or results with minor deviations which are not considered to be clinically significant in the judgment of the investigator.
  • Men of and women of childbearing potential to follow protocol defined contraception methods.
  • Women must have negative urine pregnancy test.
  • Willingness and ability to swallow study drug capsules.

Who cannot join

  • Prior or ongoing clinically significant illness, medical condition, medical history, physical findings, ECG findings, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the subject; alter the absorption, distribution, metabolism, or excretion of the study drug; or impair the assessment of study results.
  • Evidence of ongoing systemic bacterial, fungal, or viral infection (including upper respiratory tract infections).
  • Women cannot be pregnant or breast feeding.
  • Significant history of drug or alcohol abuse or addiction within 3 years before study screening or as evidenced by continuing medical complications of prior drug or alcohol use.
  • History of blood or plasma donation within 90 days before first study drug administration.
  • Currently drinking over 21 units/week of ethanol
Show all 13Show fewer
  • Drug toxicology screen positive for any prohibited drugs, illicit substances, or alcohol.
  • Anticipated need for alcohol, tobacco, or any drug during the study drug administration and immediate follow-up periods.
  • Relative to admission has any of the following exposures: has taken a prescription systemic medication within 14 days; has used an over-the counter systemic medication (other than acetaminophen) within 7 days; has ingested calcium supplements or calcium-containing vitamins within 7 days; has ingested grapefruit, grapefruit juice, or grapefruit-containing products within 7 days; has consumed alcohol within 48 hours; has taken acetaminophen within 24 hours.
  • Positive test for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen or hepatitis B core antibody, or hepatitis C antibody.
  • Unwillingness to avoid vigorous physical activity during inpatient clinic confinements.
  • Part 2 only - Inability or unwillingness to eat all of the ingredients of the high-fat, high-calorie meal as specified in the protocol.
  • Part 3 only - Known allergy to itraconazole or other azole compounds.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Celerion

    Tempe, Arizona, 85283

Other trials in United States

About this study

Official title: A Phase 1, Single-center, Open-label, Sequential Dose-Escalation Study of ACP-196 in Healthy Subjects to Evaluate Safety, Pharmacokinetics, Pharmacodynamics, Food Effects, and Drug-Drug Interactions

This study is to evaluate the safety, pharmacokinetics/pharmacodynamics (PK/PD), food-effect, and drug-drug interaction study of ACP-196 in healthy participants.

Read the detailed description

The study is divided into 3 parts. Part 1 will include 5 cohorts (Cohorts [C] 1 to 5) and participants will receive oral ACP-196 2.5 to 50 mg twice daily (BID) and 100 mg once daily (QD) on Day 1. In Part 2 (Cohort 6), participants will receive a single oral dose of 75.0 mg QD in a fasting and a fed state, with a 7-day washout period between the 2 doses. In Part 3 (Cohort 7), participants will receive a single oral dose of 50.0 mg QD alone on Day 1 and in combination with itraconazole on Day 9. Itraconazole 200 mg will be given twice daily (12 hours apart) with meals on Days 4 to 8 and once on Day 9 with ACP-196 under a fasting state in the morning.

Being tested
ACP-196, Itraconazole
Keywords
Acalabrutinib, ACP-196, Drug-drug interaction, Food effects, Healthy participants, Itraconazole, Pharmacodynamics, Pharmacokinetics, PK

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ACP-196Drug

    Also called Acalabrutinib

    Participants will receive ACP-196 oral capsule(s) in all parts.

  • ItraconazoleDrug

    Participants will receive itraconazole 200 mg capsules BID from Days 4 to 8 with meals and then 200 mg capsule QD on Day 9 under fasting state.

Study groups in NCT04901923
Study groupRoleWhat they receive
Part 1 Cohort 1ExperimentalParticipants will receive ACP-196 2.5 mg capsule orally BID on Day 1.
Receives: Drug: ACP-196
Part 1 Cohort 2ExperimentalParticipants will receive ACP-196 5 mg (2 x 2.5 mg capsules) orally BID on Day 1.
Receives: Drug: ACP-196
Part 1 Cohort 3ExperimentalParticipants will receive ACP-196 25 mg capsule orally BID on Day 1.
Receives: Drug: ACP-196
Part 1 Cohort 4ExperimentalParticipants will receive ACP-196 50 mg (2 x 25 mg capsules) orally BID on Day 1.
Receives: Drug: ACP-196
Part 1 Cohort 5ExperimentalParticipants will receive ACP-196 100 mg (4 x 25 mg capsules) orally QD on Day 1.
Receives: Drug: ACP-196
Part 2 Cohort 6ExperimentalParticipants will receive ACP-196 75 mg (3 x 25 mg capsules) orally QD on Day 1 and Day 8.
Receives: Drug: ACP-196
Part 3 Cohort 7ExperimentalParticipants will receive ACP-196 50 mg (2 x 25 mg capsules) orally QD on Day 1, itraconazole 200 mg capsules BID from Days 4 to 8 with meals and then ACP-196 50 mg (2 x 25 mg capsules) along with itraconazole 200 mg capsule QD on Day 9 under fasting state.
Receives: Drug: ACP-196; Drug: Itraconazole

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Area Under the Concentration-time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) of ACP-196 in Parts 1, 2, and 3

    Measured: Part 1: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 13, 14, 15, 16, 18, 20, 24, 36, 48, 60h; Parts 2 and 3: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72h; and till 48h on Day 8 of Part 2; and till 24h on Day 9 of Part 3

  2. Area Under the Concentration-time Curve From Time 0 to Infinity (AUC0-inf) of ACP-196 in Parts 1, 2, and 3

    Measured: Part 1: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 13, 14, 15, 16, 18, 20, 24, 36, 48, 60h; Parts 2 and 3: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72h; and till 48h on Day 8 of Part 2; and till 24h on Day 9 of Part 3

  3. Maximum Observed Plasma Concentration (Cmax) of ACP-196 in Parts 1, 2, and 3

    Measured: Part 1: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 13, 14, 15, 16, 18, 20, 24, 36, 48, 60h; Parts 2 and 3: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72h; and till 48h on Day 8 of Part 2; and till 24h on Day 9 of Part 3

  4. Time to reach Cmax (Tmax) of ACP-196 in Parts 1, 2, and 3

    Measured: Part 1: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 13, 14, 15, 16, 18, 20, 24, 36, 48, 60h; Parts 2 and 3: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72h; and till 48h on Day 8 of Part 2; and till 24h on Day 9 of Part 3

  5. Terminal-elimination Half-life (T1/2) of ACP-196 in Parts 1, 2, and 3

    Measured: Part 1: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 13, 14, 15, 16, 18, 20, 24, 36, 48, 60h; Parts 2 and 3: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72h; and till 48h on Day 8 of Part 2; and till 24h on Day 9 of Part 3

  6. Terminal-elimination Rate Constant (λz) of ACP-196 in Parts 1, 2, and 3

    Measured: Part 1: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 13, 14, 15, 16, 18, 20, 24, 36, 48, 60h; Parts 2 and 3: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72h; and till 48h on Day 8 of Part 2; and till 24h on Day 9 of Part 3

  7. Time Delay Between the Time of Dosing and the First Measurable Concentration (tlag) of ACP-196 in Parts 1, 2, and 3

    Measured: Part 1: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 13, 14, 15, 16, 18, 20, 24, 36, 48, 60h; Parts 2 and 3: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72h; and till 48h on Day 8 of Part 2; and till 24h on Day 9 of Part 3

  8. Incidences of Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

    Measured: Part 1: Day 1 through Day 3; Part 2 and Part 3: Day 1 through Day 10

  9. Incidences of Abnormal Vital Signs Reported as TEAEs

    Measured: Part 1: Day 1 ( from 1 hr predose through 1 hr postdose); Part 2: From Day 1 (1 hr predose) through Day 8 (1 hr postdose); Part 3: From Day 1 (1 hr predose) through Day 9 (1 hr postdose)

  10. Incidences of Abnormal Clinical Laboratory Parameters Reported as TEAEs

    Measured: Part 1: From Day 1 to Day 2; Part 2 and Part 3: From Day 1 to Day 10

  11. Incidences of Abnormal Electrocardiograms (ECGs) Reported as TEAEs

    Measured: Part 1: Day 1 ( from 1 hr predose through 1 hr postdose); Part 2: From Day 1 (1 hr predose) through Day 8 (1 hr postdose); Part 3: From Day 1 (1 hr predose) through Day 9 (1 hr postdose)

Secondary outcomes (2)
  1. Occupancy of Bruton's Tyrosine Kinase (BTK) by ACP-196 in Peripheral Blood Mononuclear Cells (PBMCs)

    The BTK occupancy will be measured by BTK occupancy assay which measures percent of BTK occupied post baseline compared to the baseline, post administration of study drug. The BTK occupancy is defined as ACP-196 active-site occupancy of > 80% at 24 hours after the first dose administration.

    Measured: 1, 3, 12, 15, and 24 hrs after first dose on Day 1

  2. Effect of ACP-196 on Biologic Markers of B-cell Function

    The pharmacodynamics of ACP-196 will be evaluated in cluster of differentiation (CD) 69/CD86 expression. It will be considered as complete inhibition when biological markers of B-cell function (CD69 and CD86) inhibition ≥ 90%.

    Measured: 1, 3, 12, 15, and 24 hrs after first dose on Day 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 May 2021
  2. Study start15 Mar 2014
  3. Primary completion22 May 2014
  4. Study completion22 May 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
59 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04901923
Sponsor's protocol ID
ACE-HV-001
Status last verified
May 2021
First submitted
6 May 2021
Last updated
26 May 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing ACP-196 and Itraconazole in people with Healthy Participants, run by Acerta Pharma BV at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 May 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area Under the Concentration-time Curve From Time 0 to Last Quantifiable Concentration (AUC0-last) of ACP-196 in Parts 1, 2, and 3 (time frame: Part 1: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 13, 14, 15, 16, 18, 20, 24, 36, 48, 60h; Parts 2 and 3: predose; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 36, 48, 60, 72h; and till 48h on Day 8 of Part 2; and till 24h on Day 9 of Part 3). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 May 2021.

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