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An Open Label, Single Dose, Three Part Study to Assess the Effects of Rolapitant (2 mg/mL IV Solution) on the Pharmacokinetics of Digoxin; Sulfasalazine; and the Cooperstown Cocktail (Midazolam, Omeprazole, Warfarin, Caffeine, and Dextromethorphan in Healthy Subjects

Primary Purpose

Chemotherapy-induced Nausea and Vomiting

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Rolapitant

Digoxin

Sulfasalazine

Cooperstown Cocktail

About this trial

This is an interventional basic science trial for Chemotherapy-induced Nausea and Vomiting

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesAccepts Healthy Volunteers

Main Inclusion Criteria:

Subjects must be healthy males or females aged 18 to 55 years (inclusive)
Female subjects (of childbearing potential) must have a negative pregnancy test at Screening and on Day -1
Female subjects of childbearing potential must agree to use an accepted method of birth control (excluding hormonal birth control methods) before Visit 1 and to continue its use during the study and for at least 30 days after the final dose
Subjects must have a body mass index (BMI) from 18.5 to 32.0 kg/m2 (inclusive) and a weight of ≥50 kg at Screening
Subjects must be capable of understanding the informed consent after the risks and benefits of the study have been explained; subjects must be able to sign a written informed consent and be willing to comply with the protocol requirements
Subjects must be in general good health as determined by the Investigator based on pre-study medical and surgical history, physical examination [PE], and clinical laboratory tests

Main Exclusion Criteria:

Subjects who have participated in another investigational study within 30 days or 5 half-lives of the test drug's biologic activity, whichever is longer, before the time of the first study dose
Subjects who have a history of relevant allergies (including asthma, food, or drug allergies) as determined by the Investigator
Subjects who have had significant blood loss, or have donated or received ≥1 units (450 mL) of blood, within 30 days before the first study dose
Subjects who have a history of hypersensitivity to rolapitant IV or any of its excipients or who have participated in a previous rolapitant study within 6 months prior to administration of the first dose of study drug (Day 1)
Subjects with poor venous access and/or cannot tolerate venipuncture
Subjects with a history of significant complications or anxiety associated with the IV administration of medications that, in the opinion of the Investigator, could make the subject
Subjects who have a history of hypersensitivity to sulfasalazine (Part B only).

Sites / Locations

Parexel Early Phase Unit

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Part A

Part B

Part C

Arm Description

Rolapitant IV and Digoxin

Rolapitant IV and Sulfasalazine

Rolapitant IV and Cooperstown Cocktail

Outcomes

Primary Outcome Measures

AUC: area under the plasma concentration-time curve

To evaluate the effect of Rolapitant on the PK of probe substrates

Cmax = observed maximum plasma concentration

To evaluate the effect of Rolapitant on the PK of probe substrates

Secondary Outcome Measures

Number of participants with adverse events

To evaluate the safety and tolerability of combination administration of the P-gp substrate (digoxin), the BCRP substrate (sulfasalazine), and CYP probe substrates (midazolam, omeprazole, warfarin, caffeine, and dextromethorphan [Cooperstown Cocktail]) with a single dose of rolapitant IV in a healthy adult population, as assessed by incidence and severity of AEs.

Full Information

NCT ID

NCT02434861

First Posted

April 30, 2015

Last Updated

August 21, 2015

Sponsor

Tesaro, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT02434861

Brief Title

An Open Label, Single Dose, Three Part Study to Assess the Effects of Rolapitant (2 mg/mL IV Solution) on the Pharmacokinetics of Digoxin; Sulfasalazine; and the Cooperstown Cocktail (Midazolam, Omeprazole, Warfarin, Caffeine, and Dextromethorphan in Healthy Subjects

Official Title

An Open Label, Single Dose, Three Part Study to Assess the Effects of Rolapitant (1.8 mg/mL Rolapitant IV Solution) on the Pharmacokinetics of Digoxin (P-gp); Sulfasalazine (BCRP); and the Cooperstown Cocktail (Midazolam [CYP3A4], Omeprazole [CYP2C19], Warfarin [CYP2C9], Caffeine [CYP1A2], and Dextromethorphan [CYP2D6]) in Healthy Subjects

Study Type

Interventional

2. Study Status

Record Verification Date

August 2015

Overall Recruitment Status

Completed

Study Start Date

May 2015 (undefined)

Primary Completion Date

July 2015 (Actual)

Study Completion Date

August 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Tesaro, Inc.

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

The objective of this Open Label Study is to evaluate effects of Rolapitant IV solution, and its metabolite, on the pharmacokinetics (PK) of the P-gp substrate (digoxin), the BCRP substrate (sulfasalazine), and multiple cytochrome P450 (CYP) probe substrates in a healthy adult population.

Detailed Description

Part A will compare the PK of oral digoxin alone and in combination with an IV infusion of rolapitant. Part B will compare the PK of an oral dose of sulfasalazine alone to the PK of an oral dose of sulfasalazine in combination with an IV infusion of rolapitant Part C will compare the PK of an oral dose of the Cooperstown Cocktail (midazolam, omeprazole, warfarin, caffeine, and dextromethorphan) alone and when given in combination with an IV infusion of rolapitant.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chemotherapy-induced Nausea and Vomiting

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

102 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part A

Arm Type

Experimental

Arm Description

Rolapitant IV and Digoxin

Arm Title

Part B

Arm Type

Experimental

Arm Description

Rolapitant IV and Sulfasalazine

Arm Title

Part C

Arm Type

Experimental

Arm Description

Rolapitant IV and Cooperstown Cocktail

Intervention Type

Drug

Intervention Name(s)

Rolapitant

Intervention Type

Drug

Intervention Name(s)

Digoxin

Intervention Description

P-gp substrate

Intervention Type

Drug

Intervention Name(s)

Sulfasalazine

Intervention Description

BCRP substrate

Intervention Type

Drug

Intervention Name(s)

Cooperstown Cocktail

Intervention Description

Midazolam, omeprazole, warfarin, caffeine, and dextromethorphan

Primary Outcome Measure Information:

Title

AUC: area under the plasma concentration-time curve

Description

To evaluate the effect of Rolapitant on the PK of probe substrates

Time Frame

Predose - up to 120 hours postdose

Title

Cmax = observed maximum plasma concentration

Description

To evaluate the effect of Rolapitant on the PK of probe substrates

Time Frame

Predose - up to 120 hours postdose

Secondary Outcome Measure Information:

Title

Number of participants with adverse events

Description

Time Frame

0 - 38 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

Main Inclusion Criteria: Subjects must be healthy males or females aged 18 to 55 years (inclusive) Female subjects (of childbearing potential) must have a negative pregnancy test at Screening and on Day -1 Female subjects of childbearing potential must agree to use an accepted method of birth control (excluding hormonal birth control methods) before Visit 1 and to continue its use during the study and for at least 30 days after the final dose Subjects must have a body mass index (BMI) from 18.5 to 32.0 kg/m2 (inclusive) and a weight of ≥50 kg at Screening Subjects must be capable of understanding the informed consent after the risks and benefits of the study have been explained; subjects must be able to sign a written informed consent and be willing to comply with the protocol requirements Subjects must be in general good health as determined by the Investigator based on pre-study medical and surgical history, physical examination [PE], and clinical laboratory tests Main Exclusion Criteria: Subjects who have participated in another investigational study within 30 days or 5 half-lives of the test drug's biologic activity, whichever is longer, before the time of the first study dose Subjects who have a history of relevant allergies (including asthma, food, or drug allergies) as determined by the Investigator Subjects who have had significant blood loss, or have donated or received ≥1 units (450 mL) of blood, within 30 days before the first study dose Subjects who have a history of hypersensitivity to rolapitant IV or any of its excipients or who have participated in a previous rolapitant study within 6 months prior to administration of the first dose of study drug (Day 1) Subjects with poor venous access and/or cannot tolerate venipuncture Subjects with a history of significant complications or anxiety associated with the IV administration of medications that, in the opinion of the Investigator, could make the subject Subjects who have a history of hypersensitivity to sulfasalazine (Part B only).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Dennis Vargo, MD

Organizational Affiliation

Tesaro, Inc.

Official's Role

Study Director

Facility Information:

Facility Name

Parexel Early Phase Unit

City

Baltimor

State/Province

Maryland

ZIP/Postal Code

21225

Country

United States

12. IPD Sharing Statement

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