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

NCT03994211 | Completed Phase 1 Results

• 2 other identifiers: BGB-290-1052019-000112-28
• Study Type: interventional
• Target: 25
• Locations: 4 countries
• Sites: 4

Brief 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.

Conditions

Solid Tumor

Outcome Measures

Primary Outcomes (18)

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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

• 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 Outcomes (2)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  From the date informed consent has been signed until last study medication dose plus 30 days (up to approximately 26 months)

• Number of Participants With Clinically Significant Abnormalities in Laboratory Assessments, Vital Signs, ECG Parameters and Physical Examinations

  Up to approximately 26 months

Study Arms (3)

Part A (core phase)

EXPERIMENTAL

60 mg pamiparib administered orally on Days 1 and 10 fasting 8 hours pre-dose 600 mg rifampin once a day from days 3 to 11 in the fasted state (at least 2 hours predose)

Drug: pamiparib 60 mg; Drug: rifampin

Part B (core phase)

EXPERIMENTAL

Single dose of 20 mg pamiparib orally in the fasted state (at least 8 hours predose) on days 1 and 7 200 mg itraconazole once a day approximately 30 minutes after completing a meal Day 3 to day 8

Drug: pamiparib 20 mg; Drug: itraconazole

Extension phase

EXPERIMENTAL

60 mg pamiparib orally twice a day in 28-day cycles until progression of disease

Drug: pamiparib

Interventions

pamiparib 60 mg DRUG

Single dose of 60 mg pamiparib orally on Days 1 and 10

Part A (core phase)

pamiparib 20 mg DRUG

Single dose of 20 mg pamiparib orally on days 1 and 7

Part B (core phase)

itraconazole DRUG

200 mg itraconazole once a day al Day 3 to day 8

Part B (core phase)

rifampin DRUG

600 mg rifampin once a day from days 3 to 11

Part A (core phase)

pamiparib DRUG

60 mg pamiparib orally twice a day in 28-day cycles

Extension phase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• 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.
• Disease that is evaluable per RECIST Version 1.1 or Prostate Cancer Working Group-3 (PCWG-3)
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
• Life expectancy ≥ 12 weeks
• Adequate hematologic and end-organ function

You may not qualify if:

• History of hypersensitivity to rifampin, any rifamycin or any of the components of the rifampin capsule (Part A).
• History of hypersensitivity to itraconazole or any of the components of the itraconazole capsule (Part B).
• 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
• Diagnosis of Myelodysplastic syndrome (MDS)
• Active infection requiring systemic treatment
• Any of the following cardiovascular criteria:
• Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily living, ≤ 28 days before Day 1 of pamiparib administration
• Symptomatic pulmonary embolism ≤ 28 days before Day 1 of pamiparib administration
• Any history of acute myocardial infarction ≤ 6 months before Day 1 of pamiparib administration
• 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)
• Any event of ventricular arrhythmia ≥ Grade 2 in severity ≤ 6 months before Day 1 of pamiparib administration
• Any history of cerebral vascular accident ≤ 6 months before Day 1 of pamiparib administration
• Previous complete gastric resection or lap-band surgery, chronic diarrhea, active inflammatory gastrointestinal disease, known diverticular disease or any other disease-causing malabsorption syndrome

Sponsors & Collaborators

• BeiGene: lead

Study Sites (4)

Arensia Exploratory Medicine Llc

Tbilisi, 0112, Georgia

Location

Republican Clinical Hospital, Oncology Department

Chiinu, 2025, Moldova

Location

Szpital Luxmed

Warsaw, 02-801, Poland

Location

Summit Clinical Research, Sro

Bratislava, 83101, Slovakia

Location

Related 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 solid tumors: an open-label, parallel-group phase 1 study. Cancer Chemother Pharmacol. 2021 Jul;88(1):81-88. doi: 10.1007/s00280-021-04253-x. Epub 2021 Mar 27.

  PMID: 33772633 RESULT

MeSH Terms

Interventions

pamiparib; Itraconazole; Rifampin

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: BeiGene

clinicaltrials@beigene.com

+1-877-828-5568

Study Officials

• Study Director

  BeiGene

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2019
• First Posted: June 21, 2019
• Study Start: May 29, 2019
• Primary Completion: October 25, 2019
• Study Completion: August 6, 2021
• Last Updated: October 26, 2024
• Results First Posted: May 23, 2023

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share

Locations

PL (1); GE (1); MO (1); SL (1)