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

• Sponsor: Tesaro, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02434861
• Collaborator: (none)
• Enrollment: 102
• Location: 1
• Arms: 3
• Duration (Months): 3
• Patients Per Site Per Month: 33.7

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Chemotherapy-induced Nausea and Vomiting	Drug: Rolapitant; Drug: Digoxin; Drug: Sulfasalazine; Drug: Cooperstown Cocktail	Phase 1

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 102 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• 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 Start Date: May 1, 2015
• Actual Primary Completion Date: Jul 1, 2015
• Actual Study Completion Date: Aug 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part A Rolapitant IV and Digoxin	Drug: Rolapitant; Drug: Digoxin; P-gp substrate
Experimental: Part B Rolapitant IV and Sulfasalazine	Drug: Rolapitant; Drug: Sulfasalazine; BCRP substrate
Experimental: Part C Rolapitant IV and Cooperstown Cocktail	Drug: Rolapitant; Drug: Cooperstown Cocktail; Midazolam, omeprazole, warfarin, caffeine, and dextromethorphan

Outcome Measures

Primary Outcome Measures

1. AUC: area under the plasma concentration-time curve [Predose - up to 120 hours postdose]

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

2. Cmax = observed maximum plasma concentration [Predose - up to 120 hours postdose]

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

Secondary Outcome Measures

1. Number of participants with adverse events [0 - 38 days]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 55 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Parexel Early Phase Unit	Baltimor	Maryland	United States	21225

Sponsors and Collaborators

• Tesaro, Inc.

Investigators

• Study Director: Dennis Vargo, MD, Tesaro, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Tesaro, Inc.
• ClinicalTrials.gov Identifier: NCT02434861
• Other Study ID Numbers: PR-11-5021-C
• First Posted: May 5, 2015
• Last Update Posted: Aug 25, 2015
• Last Verified: Aug 1, 2015

• Additional relevant MeSH terms: Vomiting; Sulfasalazine; Digoxin; Rolapitant

Study Results

No Results Posted as of Aug 25, 2015