A Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Drug Interaction Potential of Napabucasin in Healthy Volunteers

A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Drug Interaction Potential of Napabucasin in Healthy Volunteers

This is a phase I, single-center, open-label, single-sequence, 3-period, PK drug interaction study evaluating the effect of napabucasin in healthy volunteers on the single-dose PK of several cytochrome P450 (CYP450) probe drugs as well as a BCRP substrate.

Study Overview

• Status: Completed
• Conditions: Drug-drug Interactions
• Intervention / Treatment: Drug: napabucasin; Drug: cytochrome P450 (CYP450) probe drugs or BCRP transporter substrate

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • DeLand, Florida, United States, 32720
      • Accel Research Sites

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria

A subject will be eligible for inclusion in this study only if all the following criteria apply:

1. An Institutional Review Board (IRB) approved informed consent is signed and dated prior to any study-related activities.
2. Subject is between the ages of 18 and 45 years, inclusive.
3. Subject is a female of childbearing potential with a negative pregnancy test or has documented surgical sterilization or is post-menopausal prior to Screening. All male and female subjects must agree to use contraception while participating in the study and for 30 days after their last dose of study drug unless surgically sterile or post-menopausal.. It is the Investigator's responsibility for determining whether the Subject has adequate birth control for study participation.
4. Subject has a body mass index between 18 and 34 kg/m^2 (weight/[height]^2).
5. Subject has normal (or abnormal and clinically insignificant according to the Investigator) laboratory values at screening.
6. Subject is medically normal with no significant abnormalities at the baseline physical examination.
7. Subject has the ability to understand the requirements of the study and a willingness to comply with all study procedures.
8. Subject has not consumed and agrees to abstain from taking any dietary supplements, herbal products, or non-prescription drugs (except as authorized by the Investigator and Medical Monitor) for 14 days prior to CRU admission through Follow-Up.
9. Subject has not consumed and agrees to abstain from taking any prescription drugs (except as authorized by the Investigator and Medical Monitor) during the 14 days prior to CRU admission through Follow-Up.
10. Subject has not consumed alcohol-containing beverages for 3 days prior to CRU admission and agrees not to consume alcohol through Follow-Up.
11. Subject has not consumed grapefruit, grapefruit juice, Seville oranges, and grapefruit- or Seville orange containing products within the 14 days prior to CRU admission and agrees not to consume grapefruit or grapefruit juice through Follow-Up.
12. Subject has not used tobacco- and nicotine-containing products within 2 months prior to the CRU admission and agrees to abstain from using tobacco- and nicotine-containing products through Follow-up.
13. Subject agrees to abstain from consuming caffeine- or chocolate-containing products from 3 days prior to CRU admission through Follow-up.

Exclusion Criteria

A Subject will not be eligible for inclusion in this study if any of the following criteria apply:

1. Subject has a history illicit drug abuse in the past year or current evidence of such abuse in the opinion of the Investigator.
2. Subject has positive findings on urine drug screen.
3. Subject is positive for human immunodeficiency virus (HIV), hepatitis B and/or hepatitis C on Screening assessments.
4. Subject is determined to be a poor metabolizer for CYP2C19, CYP2C9 and/or CYP2D6.
5. Subject has a QTcF >450 msec (if male) or >470 msec (if female) at Screening.
6. Subject is pregnant or lactating.
7. Subject has an acute illness within 1 week of CRU admission.
8. Subject has a hypersensitivity or allergy to napabucasin or any of the probe drugs, or the ingredients of napabucasin or any of the probe drugs, or other clinically significant allergies.
9. Subject has donated plasma within 7 days of drug administration.
10. Subject has donated 1 or more pints of blood (or equivalent blood loss) within 30 days prior to drug administration.
11. Subject has a history of chronic Gastroesophageal reflux disease (GERD) or has used omeprazole or other proton pump inhibitors within 3 months of Screening.
12. Subject has participated in an investigational drug study within the 30 days prior to CRU admission.
13. Subject is an employee of the Investigator or study center, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, or a family member of the employees or the Investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Single-sequence 3-period; Period 1: napabucasin 240 mg BID on days 1-2 Period 2: cytochrome P450 probe drugs during days 1-4 Period 3: napabucasin 240 mg BID on days 1-11, cytochrome P450 probe drugs during days 6-9

Drug: napabucasin; Napabucasin will be administered at dose of 240 mg twice daily, every 12 hours (BID) on days 1-2 in period 1, and on days 1-11 in period 3.; Other Names: BBI-608; BBI608; Drug: cytochrome P450 (CYP450) probe drugs or BCRP transporter substrate; CYP450 probe drugs or BCRP transporter substrate will be administered once every period during days 1-4 in period 2, and days 6-9 in period 3.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pharmacokinetics for napabucasin by assessing plasma concentration	Predose and up to 7 days post dose
Pharmacokinetics for probe drugs by assessing plasma concentration	Predose and up to 7 days post dose

Collaborators and Investigators

• Sponsor: Sumitomo Pharma America, Inc.

Publications and helpful links

General Publications

• Dai X, Karol MD, Hitron M, Hard ML, Goulet MT, McLaughlin CF, Brantley SJ. Napabucasin Drug-Drug Interaction Potential, Safety, Tolerability, and Pharmacokinetics Following Oral Dosing in Healthy Adult Volunteers. Clin Pharmacol Drug Dev. 2021 Aug;10(8):824-839. doi: 10.1002/cpdd.961. Epub 2021 Jun 9.

Study record dates

Study Major Dates

• Study Start (Actual): June 30, 2017
• Primary Completion (Actual): January 23, 2018
• Study Completion (Actual): January 23, 2018

Study Registration Dates

• First Submitted: January 19, 2018
• First Submitted That Met QC Criteria: January 24, 2018
• First Posted (Actual): January 26, 2018

Study Record Updates

• Last Update Posted (Estimated): November 14, 2023
• Last Update Submitted That Met QC Criteria: November 13, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers
• Other Study ID Numbers: BBI608-102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No