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

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

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.

Study Overview

• Status: Completed
• Conditions: Chemotherapy-induced Nausea and Vomiting
• Intervention / Treatment: Drug: Rolapitant; Drug: Digoxin; Drug: Sulfasalazine; Drug: Cooperstown Cocktail

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 Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimor, Maryland, United States, 21225
      • Parexel Early Phase Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC: area under the plasma concentration-time curve	To evaluate the effect of Rolapitant on the PK of probe substrates	Predose - up to 120 hours postdose
Cmax = observed maximum plasma concentration	To evaluate the effect of Rolapitant on the PK of probe substrates	Predose - up to 120 hours postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	0 - 38 days

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): July 1, 2015
• Study Completion (Actual): August 1, 2015

Study Registration Dates

• First Submitted: April 30, 2015
• First Submitted That Met QC Criteria: May 4, 2015
• First Posted (Estimate): May 5, 2015

Study Record Updates

• Last Update Posted (Estimate): August 25, 2015
• Last Update Submitted That Met QC Criteria: August 21, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Vomiting; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Anti-Infective Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Gastrointestinal Agents; Protective Agents; Cardiotonic Agents; Neurokinin-1 Receptor Antagonists; Digoxin; Sulfasalazine; Rolapitant
• Other Study ID Numbers: PR-11-5021-C