NCT04958226

Brief Summary

This is an open-label, fixed-sequence study to evaluate the effect of capivasertib on the pharmacokinetics (PK) of midazolam, a sensitive CYP3A substrate. The PK of midazolam will be assessed when administered alone and in combination with repeated doses of capivasertib.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
21

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Oct 2021

Geographic Reach
1 country

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 1, 2021

Completed
11 days until next milestone

First Posted

Study publicly available on registry

July 12, 2021

Completed
3 months until next milestone

Study Start

First participant enrolled

October 15, 2021

Completed
1.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 6, 2023

Completed
9 days until next milestone

Study Completion

Last participant's last visit for all outcomes

February 15, 2023

Completed
Last Updated

January 25, 2024

Status Verified

January 1, 2024

Enrollment Period

1.3 years

First QC Date

July 1, 2021

Last Update Submit

January 24, 2024

Conditions

Solid Tumour

Keywords

CYP3A inhibitorPharmacokineticsSafety

Outcome Measures

Primary Outcomes (2)

  • Midazolam AUCinf

    Area under the plasma concentration-time curve from zero to infinity

    Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9, Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days)

  • Midazolam Cmax

    Maximum observed plasma (peak) drug concentration

    Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9, Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days)

Secondary Outcomes (15)

  • Midazolam AUClast

    Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9, Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days)

  • Midazolam t½λz

    Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9, Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days)

  • Midazolam tmax

    Cycle 1 Day 1, Cycle 1 Day 2, Cycle 1 Day 8, Cycle 1 Day 9, Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days)

  • Capivasertib Ctrough

    Cycle 1 Day 9 and Cycle 1 Day 13 (Cycle 1 is 29 days)

  • Capivasertib Cmax

    Cycle 1 Day 12 and Cycle 1 Day 13 (Cycle 1 is 29 days)

  • +10 more secondary outcomes

Study Arms (1)

Treatment (Midazolam + Capivasertib)

EXPERIMENTAL

Midazolam will be administered on Cycle 1 Day 1 and Cycle 1 Day 8. Capivasertib will be administrated from Cycle 1 Day 2 as an intermittent schedule (4 days on/3 days off) until discontinuation. On Cycle 1 Day 12, Midazolam will be administrated with Capivasertib.

Drug: CapivasertibDrug: Midazolam

Interventions

CapivasertibDRUG

Capivasertib (tablet) will be given as an intermittent schedule (4 days on/3 days off) from Cycle 1 Day 2 until discontinuation. Capivasertib will be administrated in both Part A and Part B.

Treatment (Midazolam + Capivasertib)
MidazolamDRUG

Single doses of midazolam (syrup, 1 mg) will be given on cycle 1 Days 1, 8, and 12.

Treatment (Midazolam + Capivasertib)

Eligibility Criteria

Age18 Years - 130 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Participants with documented evidence of locally advanced inoperable or metastatic solid tumours who may be suitable to receive capivasertib treatment.
  • Eastern Cooperative Oncology Group/World Health Organization performance status 0 to 1 and with minimum life expectancy for 12 weeks.
  • Participant should have at least one lesion that can be assessed by computed tomography/magnetic resonance imaging or plain X-ray at baseline.
  • Body mass index within the range 18 to 32 kg/m\^2

You may not qualify if:

  • Participants are excluded from the study if any of the following criteria apply:
  • Radiotherapy with a wide field of radiation within 4 weeks of the first dose of capivasertib and/or radiotherapy with a limited field of radiation for palliation within 2 weeks prior to study intervention initiation.
  • Participants with diabetes mellitus type I or participants with diabetes mellitus type II requiring insulin treatment.
  • Undergone a major surgery within 4 weeks of the first dose of capivasertib.
  • Any unresolved toxicities from prior therapies higher than CTCAE grade 2 or any unresolved toxicity that may interfere with PK assessment at the time of study intervention initiation.
  • Participants with spinal cord compression or brain metastases.
  • Participants with severe or uncontrolled systemic diseases, active bleeding diatheses, or active infection.
  • Previous allogeneic bone marrow transplant or solid organ transplant.
  • Known immunodeficiency syndrome.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Research Site

Aurora, Colorado, 80045, United States

Location

Research Site

Durham, North Carolina, 27710, United States

Location

Research Site

Cleveland, Ohio, 44106, United States

Location

Research Site

Pittsburgh, Pennsylvania, 15232, United States

Location

Research Site

Dallas, Texas, 75251, United States

Location

Related Publications (1)

  • Miller C, Sommavilla R, O'Bryant CL, Barve M, Dowlati A, Luke JJ, Khatun M, Morris T, Cullberg M. Pharmacokinetic study of capivasertib and the CYP3A4 substrate midazolam in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2024 Aug;94(2):223-235. doi: 10.1007/s00280-024-04667-3. Epub 2024 Apr 20.

    PMID: 38643311DERIVED

MeSH Terms

Interventions

capivasertibMidazolam

Intervention Hierarchy (Ancestors)

BenzodiazepinesBenzazepinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Design

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

Study Record Dates

First Submitted

July 1, 2021

First Posted

July 12, 2021

Study Start

October 15, 2021

Primary Completion

February 6, 2023

Study Completion

February 15, 2023

Last Updated

January 25, 2024

Record last verified: 2024-01

Data Sharing

IPD Sharing
Will share

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. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

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 deidentified 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.
More information

Locations

US(5)