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

Chemotherapy-induced Nausea and Vomiting Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02434861
• Other study ID #: PR-11-5021-C
• Status: Completed
• Phase: Phase 1
• First received: April 30, 2015
• Last updated: August 21, 2015
• Start date: May 2015
• Est. completion date: August 2015

Study information

• Verified date: August 2015
• Source: Tesaro, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 102
• Est. completion date: August 2015
• Est. primary completion date: July 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Chemotherapy-induced Nausea and Vomiting

Intervention

Drug:
• Rolapitant

• Digoxin
P-gp substrate
• Sulfasalazine
BCRP substrate
• Cooperstown Cocktail
Midazolam, omeprazole, warfarin, caffeine, and dextromethorphan

Locations

Country	Name	City	State
United States	Parexel Early Phase Unit	Baltimor	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Tesaro, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	Cmax = observed maximum plasma concentration	To evaluate the effect of Rolapitant on the PK of probe substrates	Predose - up to 120 hours postdose	No
Secondary	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	No