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

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Part C	Cooperstown Cocktail	Rolapitant IV and Cooperstown Cocktail
Part A	Digoxin	Rolapitant IV and Digoxin
Part C	Rolapitant	Rolapitant IV and Cooperstown Cocktail
Part B	Rolapitant	Rolapitant IV and Sulfasalazine
Part A	Rolapitant	Rolapitant IV and Digoxin
Part B	Sulfasalazine	Rolapitant IV and Sulfasalazine

Primary Outcome Measures

Name	Time	Method
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
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

Name	Time	Method
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.

Recruitment & Eligibility