Description:
This will be a Phase 1, open label, 2-sequence, crossover study to establish the BE of the
current commercial formulation (Generation 3.1 talazoparib capsules) to the proposed
talazoparib liquid-filled soft gelatin capsule (soft gel capsule) formulation after multiple
dosing under fasting conditions in participants with advanced solid tumors. In addition, the
effect of food on the PK of the proposed talazoparib soft gel capsule formulation will be
evaluated in fixed sequence after the 2 BE assessment periods.
Title
- Brief Title: A Bioequivalence Study Between the Proposed and Current Talazoparib Capsule Formulation and Food Effect Study for the Proposed Talazoparib Capsule Formulation in Participants With Advanced Solid Tumors
- Official Title: A PHASE 1, OPEN LABEL, CROSSOVER STUDY TO ESTABLISH BIOEQUIVALENCE BETWEEN THE PROPOSED SOFT GEL TALAZOPARIB CAPSULE FORMULATION AND THE CURRENT TALAZOPARIB COMMERCIAL FORMULATION AND TO ESTIMATE THE FOOD EFFECT ON PHARMACOKINETICS OF THE PROPOSED TALAZOPARIB SOFT GEL CAPSULE FORMULATION IN PARTICIPANTS WITH ADVANCED SOLID TUMORS
Clinical Trial IDs
- ORG STUDY ID:
C3441037
- SECONDARY ID:
2020-006101-35
- NCT ID:
NCT04672460
Conditions
Interventions
Drug | Synonyms | Arms |
---|
TALZENNA capsule | | Sequence 1 |
Talazoparib soft gel capsule | | Sequence 1 |
Talazoparib soft gel capsule | | Sequence 1 |
Purpose
This will be a Phase 1, open label, 2-sequence, crossover study to establish the BE of the
current commercial formulation (Generation 3.1 talazoparib capsules) to the proposed
talazoparib liquid-filled soft gelatin capsule (soft gel capsule) formulation after multiple
dosing under fasting conditions in participants with advanced solid tumors. In addition, the
effect of food on the PK of the proposed talazoparib soft gel capsule formulation will be
evaluated in fixed sequence after the 2 BE assessment periods.
Trial Arms
Name | Type | Description | Interventions |
---|
Sequence 1 | Experimental | Participants receive Treatment B for 28 days, followed by Treatment A for 21 days, followed by Treatment C for 21 days. | - TALZENNA capsule
- Talazoparib soft gel capsule
- Talazoparib soft gel capsule
|
Sequence 2 | Experimental | Participants receive Treatment A for 28 days, followed by Treatment B for 21 days, followed by Treatment C for 21 days. | - TALZENNA capsule
- Talazoparib soft gel capsule
- Talazoparib soft gel capsule
|
Eligibility Criteria
Inclusion Criteria
1. Histological diagnosis of recurrent, locally advanced or metastatic solid tumor that
is not amenable for treatment with curative intent.
- Solid tumors with known or likely pathogenic germline or somatic tumor gene
defect (eg, one or more BRCA1 or BRCA2 gene defect except for ovarian cancer)
that would benefit from PARPi therapy per current approvals for the tumor
indication or supported by strong scientific evidence.
- Received at least 1 prior SOC regimen, if it exists, as appropriate for the
respective tumor type unless deemed unsuitable or declined these therapies;
ovarian cancer participants must have at least 1 prior cytotoxic chemotherapy
regimen, including at least 1 course of platinum-based therapy. Participants must
not have had disease progression within 6 months of initiation of platinum
containing regimen.
2. ECOG performance score of 0-1.
3. Adequate organ function:
- ANC ≥1500 cells/mm3
- Platelets ≥100,000 cells/mm3
- Hemoglobin ≥10.0 g/dL
- CLCR ≥60 mL/min and no documented CLCR <60 mL/min and no change in CLCR >25% in
the past 4 weeks
- AST and ALT ≤2.5 × ULN; if liver function abnormalities are due to hepatic
metastasis, then AST and ALT ≤5 × ULN;
- Total bilirubin ≤1.5 × ULN (≤3 × ULN for Gilbert's syndrome);
Exclusion Criteria
1. For ovarian participants: Non-epithelial tumors or ovarian tumors with low malignant
potential (ie, borderline tumors) or mucinous tumors.
2. Toxicities from previous anti-cancer therapies must be resolved to NCI CTCAE <Grade 2,
except for alopecia, sensory neuropathies ≤Grade 2, or other Grade ≤2 AEs not
constituting a safety risk, based on investigator's judgment, are acceptable.
3. Diagnosed with MDS or AML.
4. Active infection requiring systemic therapy within 2 weeks of enrollment.
5. Any condition in which active bleeding or pathological conditions may carry a high
risk of bleeding (eg, known bleeding disorder, coagulopathy or tumor involvement with
major vessels).
6. Known or suspected brain metastasis or active leptomeningeal disease undergoing or
requiring treatment. Asymptomatic brain metastases currently not undergoing treatment
are allowed.
7. Known history of testing positive for HIV, AIDS, positive HBV surface antigen,
positive HCV RNA, or positive COVID-19 viral test. Asymptomatic patients with no
active infection detected but positive antibody tests, indicating past infection, are
allowed.
8. Current or anticipated use of P-gp inhibitors, BCRP inhibitors, and P-gp inducers
within 2 weeks or 5 half-lives prior to randomization (whichever is longer) .
Maximum Eligible Age: | 70 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | AUC24 of all talazoparib treatment |
Time Frame: | 24 hours [On Day 28 for Period 1 and on Day 21 for Periods 2 and 3] |
Safety Issue: | |
Description: | Area under the plasma concentration-time curve from time 0 to 24 hours |
Secondary Outcome Measures
Measure: | Tmax of all talazoparib treatment |
Time Frame: | 24 hours [On Day 28 for Period 1 and on Day 21 for Periods 2 and 3] |
Safety Issue: | |
Description: | Time for Cmax |
Measure: | Ctrough of all talazoparib treatment |
Time Frame: | 24 hours [On Day 27 for Period 1 and on Day 20 for Periods 2] |
Safety Issue: | |
Description: | Predose plasma drug concentration |
Measure: | CL/F of all talazoparib treatment |
Time Frame: | 24 hours [On Day 28 for Period 1 and on Day 21 for Periods 2 and 3] |
Safety Issue: | |
Description: | Apparent clearance after oral dose |
Measure: | AUClast of all talazoparib treatment |
Time Frame: | 24 hours [On Day 28 for Period 1 and on Day 21 for Periods 2 and 3] |
Safety Issue: | |
Description: | Area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (Clast) |
Measure: | Safety and tolerability of the proposed talazoparib soft gel capsule formulation |
Time Frame: | Approximately 4 years |
Safety Issue: | |
Description: | Incidence of AEs characterized by type, severity (graded by NCI CTCAE version 5.0), timing, seriousness and relationship to study treatment |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Pfizer |
Trial Keywords
- PARP inhibitor
- Talazoparib
- Talzenna
- Pharmacokinetics
Last Updated
August 18, 2021