A Phase 1, 2-Part, Single Ascending Dose Assessment of the Safety, Tolerability, and Pharmacokinetics of Rolapitant Intravenous in Healthy Volunteers

The purpose of this study is to assess the safety and tolerability of single increasing doses of intravenously administered rolapitant in healthy male and female subjects.

Study Overview

• Status: Completed
• Conditions: Chemotherapy-induced Nausea and Vomiting
• Intervention / Treatment: Drug: Rolapitant

Detailed Description

Part 1 of the study is designed to evaluate the safety and tolerability of a SAD, up to 6 cohorts,of rolapitant IV (2 mg/mL solution) administered as an IV infusion over 30 minutes.

In Part 2 of the study, the safety and tolerability of the highest safe and well-tolerated dose established in Part 1 will be evaluated in an expanded cohort. The highest safe and well-tolerated dose established in Part 1 will be ascertained by the following criteria: an upper limit of 90% confidence interval (CI) for Cmax. A minimum of 40 subjects will be enrolled in Part 2.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21225
      • Parexel

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:

• Subject must be a healthy male or female aged 18 to 55 years at Screening
• A female subject must have a negative pregnancy test at Screening and on Day -1.
• A female subject of childbearing potential must agree to use an accepted method of birth control (excluding hormonal birth control methods) from Screening through 30 days after final study drug administration.

• Subject must have a body mass index (BMI) from 18.5 to 32.0 kg/m2 and a weight of

  ≥ 50 kg at Screening.

• Subject must be able to provide informed consent after risks and benefits have been explained. Subject must also be willing and able to comply with the protocol requirements.
• Subject must be in general good health as determined by the Investigator based on pre-study medical, medication, and surgical history; physical examination; and clinical laboratory tests.

Main Exclusion Criteria:

• Subject must not have been dosed with test drug or blinded study drug in another investigational study within 30 days or 5 half-lives of the biologic activity of the test drug, whichever is longer, before the time of first study dose.
• Subject must not have a history of hypersensitivity to rolapitant IV or any of its excipients or who have completed a study visit as part of a previous rolapitant study within the 6 months prior to first study drug administration (Day
• Subject must not have poor venous access or consider venipuncture intolerable.
• Subject must not have 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 unable to complete dosing requirements.
• Subject must not be pregnant or lactating.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rolapitant Cohort 1; Investigational Product: Rolapitant Dose 1 administered IV as a 30-minute infusion Dosage Form: 2 mg/mL solution	Drug: Rolapitant
Experimental: Rolapitant Cohort 2; Investigational Product: Rolapitant Dose 2 administered IV as a 30-minute infusion Dosage Form: 2 mg/mL solution	Drug: Rolapitant
Experimental: Rolapitant Cohort 3; Investigational Product: Rolapitant Dose 3 administered IV as a 30-minute infusion Dosage Form: 2 mg/mL solution	Drug: Rolapitant
Experimental: Rolapitant Cohort 4; Investigational Product: Rolapitant Dose 4 administered IV as a 30-minute infusion Dosage Form: 2 mg/mL solution	Drug: Rolapitant
Experimental: Rolapitant Cohort 5; Investigational Product: Rolapitant Dose 5 administered IV as a 30-minute infusion Dosage Form: 2 mg/mL solution	Drug: Rolapitant
Experimental: Rolapitant Cohort 6; Investigational Product: Rolapitant Dose 6 administered IV as a 30-minute infusion Dosage Form: 2 mg/mL solution	Drug: Rolapitant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1 Dose Escalation: Safety and Tolerability (adverse events)	To evaluate the safety and tolerability of rolapitant IV (30 minutes infusion) in healthy adult volunteers as assessed by the incidence and severity of AEs	0-30 days after administration of study drug
Part 2 Dose Treatment: Safety and Tolerability (adverse events)	To evaluate the safety and tolerability of rolapitant IV (30 minutes infusion) to an expanded cohort of healthy adult volunteers at the highest safe and well-tolerated dose established in Part 1 as assessed by the incidence and severity of AEs.	: 0-30 days after administration of study drug

Secondary Outcome Measures

Outcome Measure	Time Frame
1. AUC0-last: area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration	0-21 days
2. Cmax = observed maximum plasma concentration	0-21 days

Collaborators and Investigators

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

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: March 3, 2015
• First Submitted That Met QC Criteria: March 6, 2015
• First Posted (Estimate): March 9, 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; Neurokinin-1 Receptor Antagonists; Rolapitant
• Other Study ID Numbers: PR-11-5022-C