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.
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
Interventions
Drug | Synonyms | Arms |
---|
Capivasertib | | Treatment (Midazolam + Capivasertib) |
Midazolam | | Treatment (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
Name | Type | Description | Interventions |
---|
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. | |
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