Study to Investigate the Effect of Rifampin and Itraconazole on the Action of Pamiparib in Participants With Cancer

Solid Tumor Clinical Trial

Official title:

A Phase 1, Open-label, Parallel-group, Fixed-sequence Study to Investigate the Effect of the CYP3A Inducer Rifampin and the CYP3A Inhibitor Itraconazole on the Pharmacokinetics of Pamiparib (BGB-290) in Cancer Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03994211
• Other study ID #: BGB-290-105
• Secondary ID: 2019-000112-28
• Status: Completed
• Phase: Phase 1
• Start date: May 29, 2019
• Est. completion date: August 6, 2021

Study information

• Verified date: May 2023
• Source: BeiGene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study was an open-label, parallel-group, fixed-sequence study in male and female cancer patients. The study consists of 2 phases: the Core Phase, which is divided into Part A and Part B, and the Extension Phase. Part A investigated the effect of CYP3A induction by rifampin on the single dose pharmacokinetics (PK) of pamiparib, and Part B investigated the effect of CYP3A inhibition by itraconazole on the single dose PK of pamiparib. Participants were offered participation in the Extension Phase, in which they received pamiparib until progression of disease, unacceptable toxicity, withdrawal of consent, or any other reason for discontinuation.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: August 6, 2021
• Est. primary completion date: October 25, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

1. Age = 18 years

2. Histologically or cytologically confirmed advanced or metastatic solid tumors that are refractory or resistant to standard therapy or for which no suitable effective standard therapy exists.

3. Disease that is evaluable per RECIST Version 1.1 or Prostate Cancer Working Group-3 (PCWG-3)

4. Eastern Cooperative Oncology Group (ECOG) performance status = 1

5. Life expectancy = 12 weeks

6. Adequate hematologic and end-organ function

Key Exclusion Criteria:

1. History of hypersensitivity to rifampin, any rifamycin or any of the components of the rifampin capsule (Part A).

2. History of hypersensitivity to itraconazole or any of the components of the itraconazole capsule (Part B).

3. Prior treatment with a poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor at therapeutic doses is allowed, provided that such treatment was not the most recent therapy (PARP inhibitor must have been discontinued = 3 months prior to

the first dose of pamiparib):

• Participants who experienced prior severe toxicity to PARP inhibitors that in the opinion of the investigator precludes further treatment with PARP inhibitors should be excluded

4. Diagnosis of Myelodysplastic syndrome (MDS)

5. Active infection requiring systemic treatment

6. Any of the following cardiovascular criteria:

1. Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily living, = 28 days before Day 1 of pamiparib administration

2. Symptomatic pulmonary embolism = 28 days before Day 1 of pamiparib administration

3. Any history of acute myocardial infarction = 6 months before Day 1 of pamiparib administration

4. Any history of heart failure meeting New York Heart Association Classification III or IV = 6 months before Day 1 of pamiparib

• Participants with congestive heart failure or history of heart failure should be excluded from Part B (itraconazole)

5. Any event of ventricular arrhythmia = Grade 2 in severity = 6 months before Day 1 of pamiparib administration

6. Any history of cerebral vascular accident = 6 months before Day 1 of pamiparib administration

7. Previous complete gastric resection or lap-band surgery, chronic diarrhea, active inflammatory gastrointestinal disease, known diverticular disease or any other disease-causing malabsorption syndrome

• Gastroesophageal reflux disease under treatment with proton pump inhibitors is allowed

8. Active bleeding disorder, including gastrointestinal bleeding, as evidenced by hematemesis, significant hemoptysis, or melena = 6 months before Day 1 of pamiparib administration

9. Use or anticipated need for food or drugs known to be strong or moderate CYP3A inhibitors or strong CYP3A inducers = 14 days (or = 5 half-lives if half-life is known) prior to Day 1 of pamiparib administration

10. Known history of intolerance to the excipients of the pamiparib capsule

11. Have known hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• Solid Tumor

Intervention

Drug:
• pamiparib 60 mg
Single dose of 60 mg pamiparib orally on Days 1 and 10
• pamiparib 20 mg
Single dose of 20 mg pamiparib orally on days 1 and 7
• itraconazole
200 mg itraconazole once a day al Day 3 to day 8
• rifampin
600 mg rifampin once a day from days 3 to 11
• pamiparib
60 mg pamiparib orally twice a day in 28-day cycles

Locations

Country	Name	City	State
Georgia	Research Institute of Clinical Medicine	Tbilisi
Moldova, Republic of	Republican Clinical Hospital, Oncology Department	Chisinau
Poland	Szpital LuxMed	Warsaw
Slovakia	Summit Clinical Research, s.r.o.	Bratislava

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Countries where clinical trial is conducted

Georgia,  Moldova, Republic of,  Poland,  Slovakia, 

References & Publications (1)

Mu S, Lin C, Skrzypczyk-Ostaszewicz A, Bulat I, Maglakelidze M, Skarbova V, Andreu-Vieyra C, Sahasranaman S. The pharmacokinetics of pamiparib in the presence of a strong CYP3A inhibitor (itraconazole) and strong CYP3A inducer (rifampin) in patients with — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Observed Concentration (Cmax) of Pamiparib in Plasma for Part A		Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12, 24, and 48 hours post-dose
Primary	Maximum Observed Concentration (Cmax) of Pamiparib in Plasma for Part B		Part B: from Day -1 (admission) to Day 9 (discharge; ) 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12, 24, and 48 hours post-dose
Primary	AUC From Time Zero to Time of Last Quantifiable Concentration Post-dose (AUC0-tlast) in Plasma for Part A		Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12, 24, and 48 hours post-dose
Primary	AUC From Time Zero to Time of Last Quantifiable Concentration Post-dose (AUC0-tlast) in Plasma for Part B		Part B: from Day -1 (admission) to Day 9 (discharge) 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12, 24, and 48 hours post-dose
Primary	AUC From Zero to Infinity (AUC0-inf) of Pamiparib in Plasma for Part A		Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12, 24, and 48 hours post-dose
Primary	AUC From Zero to Infinity (AUC0-inf) of Pamiparib in Plasma for Part B		Part B: from Day -1 (admission) to Day 9 (discharge) 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12, 24, and 48 hours post-dose
Primary	AUC From Zero to 12 Hours (AUC0-12) of Pamiparib in Plasma for Part A		Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, and 12 hours post-dose
Primary	AUC From Zero to 12 Hours (AUC0-12) of Pamiparib in Plasma for Part B		Part B: from Day -1 (admission) to Day 9 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, and 12 hours post-dose
Primary	AUC From Zero to 9 Hours (AUC0-9) of Pamiparib in Plasma for Part A		Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, and 9 hours post-dose
Primary	AUC From Zero to 9 Hours (AUC0-9) of Pamiparib in Plasma for Part B		Part B: from Day -1 (admission) to Day 9 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, and 9 hours post-dose
Primary	Time of the Maximum Observed Concentration (Tmax) of Pamiparib for Part A		Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12 hours post-dose
Primary	Time of the Maximum Observed Concentration (Tmax) of Pamiparib for Part B		Part B: from Day -1 (admission) to Day 9 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12 hours post-dose
Primary	Apparent Terminal Elimination Half-life (t1/2) of Pamiparib in Plasma for Part A		Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12 hours post-dose
Primary	Apparent Terminal Elimination Half-life (t1/2) of Pamiparib in Plasma for Part B		Part B: from Day -1 (admission) to Day 9 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12 hours post-dose
Primary	Apparent Oral Clearance (CL/F) of Pamiparib in Plasma for Part A		Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12 hours post-dose
Primary	Apparent Oral Clearance (CL/F) of Pamiparib in Plasma for Part B		Part B: from Day -1 (admission) to Day 9 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12 hours post-dose
Primary	Apparent Volume of Distribution (Vz/F) of Pamiparib in Plasma for Part A		Part A: from Day -1 (admission) to Day 12 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12 hours post-dose
Primary	Apparent Volume of Distribution (Vz/F) of Pamiparib in Plasma for Part B		Part B: from Day -1 (admission) to Day 9 (discharge); 30 min pre-dose, 0.5, 1, 2, 4, 6, 9, 12 hours post-dose
Secondary	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	TEAE is defined as any AE with an onset date on or after the date of first dose of study medication until the date of last study medication dose plus 30 days. Seriousness of the AE is determined by the investigator based on seriousness criteria.	From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)
Secondary	Number of Participants With Clinically Significant Abnormalities in Laboratory Assessments, Vital Signs, ECG Parameters and Physical Examinations		Up to approximately 26 months