Phase 2, randomized, double-blind, Placebo-Controlled, Multiple Dose Study for the treatment of Patients with Metastatic Breast Cancer.
This is a multiple center, randomized, double-blind, Phase 2 study of NBP administered to women with metastatic breast cancer who receive nab-paclitaxel as therapy. Nab-paclitaxel will be administered at a dose \>260 mg/m2 every 3 weeks for 4 planned cycles. Subjects will begin receiving NBP orally at a dose of 400 mg administered every 12-hours (BID) or matching placebo 5 days (10 doses) prior to starting nab-paclitaxel therapy and continue to self-administer it BID until Visit 6/Day 100/Week 15. The primary objective is to evaluate the efficacy of NBP relative to placebo at preventing or reducing symptoms associated with nab-paclitaxel induced toxic neuropathy (CIPN). The secondary objectives include an evaluation the efficacy of NBP relative to placebo at preventing or attenuating taxane induced acute pain syndrome (TAPS), the evaluation of the safety and tolerability of NBP relative to placebo and to determine if NBP administration impacts the pharmacokinetics of nab-paclitaxel or if nab-paclitaxel affects the pharmacokinetics of NBP.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Take 4 capsules BID on an empty stomach at least 1 hour before food intake, and remain fasting at least 1 hour after dosing
Take 4 capsules BID on an empty stomach at least 1 hour before food intake, and remain fasting at least 1 hour after dosing.
Mean Change from Baseline in EORTC Quality of Life Questionnaire Chemotherapy-Induced Peripheral Neuropathy (EORTC QLQ-CIPN20) Sensory Subscale
Change from baseline in the mean EORTC QLQ-CIPN20 sensory subscale (converted to a 0-100 scale) collected during the treatment period at weeks 5, 8, 11 and 15.
Time frame: Baseline and weeks 5, 8, 11 and 15
Number of Participants Requiring Rescue Medication
The number and percentage of participants requiring oxycodone of any amount anytime during the 15 week treatment period.
Time frame: 15 weeks
Days Free of Rescue Medication
The mean cumulative number of days free of oxycodone of any amount anytime for each participant during the 15 week treatment period.
Time frame: 15 weeks
Mean Change from Baseline in the Brief Pain Inventory Short Form (mBPI-SF) score.
The mean change from baseline (mean days 2-7 after first dose of NBP or Placebo) in the mBPI-SF total score to mean of all post-nab-paclitaxel mBPI-SF scores collected on days 2-7 after each of 4 nab-paclitaxel administration at days 7, 28, 49 and 70 during the 15 week treatment period.
Time frame: 15 weeks
Number of Participants with Treatment-Emergent Adverse Events
The number and percentage of participants with treatment-emergent adverse events according to MedDRA system organ class and preferred term with onset during the 15 week treatment period or 4 week follow-up.
Time frame: 19 weeks
Area Under the Curve (AUC) for NBP
The AUC (h\*ng/mL) be calculated using Phoenix WinNonlin software
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Time frame: 0, 1.5, 3, 4, 6, 8 and 24 hours - Days 6 and 7
Cmax for NBP
Cmax (ng/mL) be calculated using Phoenix WinNonlin software
Time frame: Time Frame: 0, 1.5, 3, 4, 6, 8 and 24 hours - Days 6 and 7
Tmax for NBP
Tmax (hr) be calculated using Phoenix WinNonlin software
Time frame: 0, 1.5, 3, 4, 6, 8 and 24 hours - Days 6 and 7
Area Under the Curve for Paclitaxel
AUC (h\*ng/mL) be calculated using Phoenix WinNonlin software
Time frame: 0, 1.5, 3, 4, 6, 8 and 24 hours - Days 6 and 7
Cmax for Paclitaxel
Cmax (ng/mL) be calculated using Phoenix WinNonlin software
Time frame: 0, 1.5, 3, 4, 6, 8 and 24 hours - Days 6 and 7
Tmax for Paclitaxel
Tmax (hr) be calculated using Phoenix WinNonlin software
Time frame: Time Frame: 0, 1.5, 3, 4, 6, 8 and 24 hours - Days 6 and 7