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

• ClinicalTrials.gov Identifier: NCT03411122
• Recruitment Status: Completed
• First Posted: January 26, 2018
• Last Update Posted: July 21, 2020
• Sponsor: Sumitomo Dainippon Pharma Oncology, Inc
• Information provided by (Responsible Party): Sumitomo Dainippon Pharma Oncology, Inc

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Drug-drug Interactions	Drug: napabucasin; Drug: cytochrome P450 (CYP450) probe drugs or BCRP transporter substrate	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Drug Interaction Potential of Napabucasin in Healthy Volunteers
• Actual Study Start Date: June 30, 2017
• Actual Primary Completion Date: January 23, 2018
• Actual Study Completion Date: January 23, 2018

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Pharmacokinetics for napabucasin by assessing plasma concentration [ Time Frame: Predose and up to 7 days post dose ]
2. Pharmacokinetics for probe drugs by assessing plasma concentration [ Time Frame: Predose and up to 7 days post dose ]

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Florida

Accel Research Sites

DeLand, Florida, United States, 32720

Sponsors and Collaborators

Sumitomo Dainippon Pharma Oncology, Inc

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Sumitomo Dainippon Pharma Oncology, Inc
• ClinicalTrials.gov Identifier: NCT03411122
• Other Study ID Numbers: BBI608-102
• First Posted: January 26, 2018
• Last Update Posted: July 21, 2020
• Last Verified: July 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sumitomo Dainippon Pharma Oncology, Inc:

Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers