Clinical Trials /

A Study to Assess the Effect of Capivasertib on Midazolam in Patients With Advanced Solid Tumours

NCT04958226

Description:

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.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study to Assess the Effect of Capivasertib on Midazolam in Patients With Advanced Solid Tumours
  • Official Title: An Open-label, Fixed-sequence Study to Assess the Effect of Repeated Doses of Capivasertib on the Pharmacokinetics of Oral Midazolam (a CYP450 3A Probe) in Patients With Advanced Solid Tumours Harbouring Alterations in the PI3K/AKT/PTEN Pathway

Clinical Trial IDs

  • ORG STUDY ID: D3614C00003
  • NCT ID: NCT04958226

Conditions

  • Solid Tumour

Interventions

DrugSynonymsArms
CapivasertibTreatment (Midazolam + Capivasertib)
MidazolamTreatment (Midazolam + Capivasertib)

Purpose

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.

Detailed Description

      This is 2 part study: Part A and Part B. Part A of the study consists of a screening period
      and 3 treatment periods (midazolam alone, capivasertib alone, and midazolam + capivasertib).
      During Part A, the PK profile of midazolam will be determined with and without capivasertib.
      Participants who complete Part A without disease progression and unacceptable toxicity will
      proceed to Part B. Part B of the study consists of an extended treatment period with
      capivasertib alone, followed by a 30-day safety follow-up.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (Midazolam + Capivasertib)ExperimentalMidazolam 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.
  • Capivasertib
  • Midazolam

Eligibility Criteria

        Inclusion Criteria:

          1. Participants with documented evidence of locally advanced inoperable or metastatic
             solid tumours who have exhausted standard of care options and may be suitable to
             receive capivasertib monotherapy treatment with tumours harbouring a protocol
             specified alteration in the PIK3CA/AKT/PTEN genes determined by local testing.

          2. Eastern Cooperative Oncology Group/World Health Organization performance status 0 to 1
             and with minimum life expectancy for 12 weeks.

          3. Participant should have at least one lesion that can be assessed by computed
             tomography/magnetic resonance imaging or plain X-ray at baseline

          4. Body mass index within the range 18 to 30 kg/m^2

        Exclusion Criteria:

        Participants are excluded from the study if any of the following criteria apply:

          1. 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.

          2. Participants with diabetes mellitus type I or diabetes mellitus type II (irrespective
             of management).

          3. Undergone a major surgery within 4 weeks of the first dose of capivasertib.

          4. 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.

          5. Participants with spinal cord compression or brain metastases.

          6. Participants with severe or uncontrolled systemic diseases, active bleeding diatheses,
             or active infection.

          7. Previous allogeneic bone marrow transplant or solid organ transplant.

          8. Known immunodeficiency syndrome.
      
Maximum Eligible Age:130 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Midazolam AUCinf
Time Frame:Cycle 1 Day 1, Cycle 1 Day 8 and Cycle 1 Day 12 (Cycle 1 is 29 days)
Safety Issue:
Description:Area under the plasma concentration-time curve from zero to infinity

Secondary Outcome Measures

Measure:Midazolam AUClast
Time Frame:Cycle 1 Day 1, Cycle 1 Day 8 and Cycle 1 Day 12 (Cycle 1 is 29 days)
Safety Issue:
Description:Area under plasma concentration-time curve from zero to the last quantifiable concentration
Measure:Midazolam t½λz
Time Frame:Cycle 1 Day 1, Cycle 1 Day 8 and Cycle 1 Day 12 (Cycle 1 is 29 days)
Safety Issue:
Description:Half-life associated with terminal slope (λz) of a semilogarithmic concentration-time curve
Measure:Midazolam tmax
Time Frame:Cycle 1 Day 1, Cycle 1 Day 8 and Cycle 1 Day 12 (Cycle 1 is 29 days)
Safety Issue:
Description:Time to reach peak or maximum observed concentration
Measure:Capivasertib Ctrough
Time Frame:Cycle 1 Day 5, Cycle 1 Day 9, Cycle 1 Day 11, and Cycle 1 Day 13 (Cycle 1 is 29 days)
Safety Issue:
Description:Observed lowest drug concentration reached before the next dose is administered
Measure:Capivasertib Cmax
Time Frame:Cycle 1 Day 12 (Cycle 1 is 29 days)
Safety Issue:
Description:Maximum observed plasma (peak) drug concentration
Measure:Capivasertib AUCτ
Time Frame:Cycle 1 Day 12 (Cycle 1 is 29 days)
Safety Issue:
Description:Area under plasma concentration-time curve in the dose interval
Measure:Capivasertib t½λz
Time Frame:Cycle 1 Day 12 (Cycle 1 is 29 days)
Safety Issue:
Description:Half-life associated with terminal slope (λz) of a semilogarithmic concentration-time curve
Measure:Capivasertib tmax
Time Frame:Cycle 1 Day 12 (Cycle 1 is 29 days)
Safety Issue:
Description:Time to reach peak or maximum observed concentration
Measure:Capivasertib CL/F
Time Frame:Cycle 1 Day 12 (Cycle 1 is 29 days)
Safety Issue:
Description:Apparent total body clearance of drug from plasma after extravascular administration
Measure:Capivasertib metabolite AZ14102143 Ctrough
Time Frame:Cycle 1 Day 5, Cycle 1 Day 9, Cycle 1 Day 11, and Cycle 1 Day 13 (Cycle 1 is 29 days)
Safety Issue:
Description:Observed lowest drug concentration reached before the next dose is administered
Measure:Capivasertib metabolite AZ14102143 Cmax
Time Frame:Cycle 1 Day 12 (Cycle 1 is 29 days)
Safety Issue:
Description:Maximum observed plasma (peak) drug concentration
Measure:Capivasertib metabolite AZ14102143 AUCτ
Time Frame:Cycle 1 Day 12 (Cycle 1 is 29 days)
Safety Issue:
Description:Area under plasma concentration-time curve in the dose interval
Measure:Capivasertib metabolite AZ14102143 t½λz
Time Frame:Cycle 1 Day 12 (Cycle 1 is 29 days)
Safety Issue:
Description:Half-life associated with terminal slope (λz) of a semilogarithmic concentration-time curve
Measure:Capivasertib metabolite AZ14102143 tmax
Time Frame:Cycle 1 Day 12 (Cycle 1 is 29 days)
Safety Issue:
Description:Time to reach peak or maximum observed concentration
Measure:Number of participants with adverse events and serious adverse events
Time Frame:From screening to disease progression or discontinuation from the study (up to 15 months)
Safety Issue:
Description:Assessment of safety and tolerability of capivasertib alone and in combination with midazolam.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • CYP3A inhibitor
  • Pharmacokinetics
  • Safety

Last Updated

July 12, 2021