Study to Assess the Effect of Ketoconazole on the Pharmacokinetics of NBI-98854 in Healthy Subjects

Study Overview
=================
Brief Summary
-----------------
The purposes of this study are to: learn about the safety of the study drug (NBI-98854); learn how subjects tolerate the study drug; and evaluate and compare the pharmacokinetics (PK testing, the study of how the body absorbs, distributes, breaks down and eliminates a drug) of the investigational study drug after taking it alone and with ketoconazole. Ketoconazole is known to affect the PK of many drugs and is studied to more safely prescribe medications.

Official Title
-----------------
A Phase 1, Open-Label Study to Assess the Effect of Ketoconazole on the Pharmacokinetics of NBI-98854 in Healthy Subjects

Conditions
-----------------
Effect of Ketoconazole on the PK of NBI-98854 in Healthy Subjects

Intervention / Treatment
-----------------
* Drug: NBI-98854 50 mg capsule once daily
* Drug: Ketoconazole 400 mg (200 mg twice daily)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy male or female volunteer, 18 to 40 years of age. Subjects of childbearing potential must agree to use hormonal or two forms of nonhormonal birth control during the study. Female subjects must not be pregnant, given birth within 1 year of study start, or breastfeeding. Be in good general health and expected to complete the clinical study as designed. Have a body mass index (BMI) of 18 to 30 kg/m2 (both inclusive). Exclusion Criteria: Have an active clinically significant unstable medical condition within 1 month (30 days) prior to screening. Have a history of substance dependence or substance (drug) or alcohol abuse within the 3 months before study start. Report more than two alcoholic beverages daily or more than 14 alcoholic beverages weekly withing 7 days of study start. Report use of tobacco and/or nicotine-containing products within 3 months of study start. Have a known history of neuroleptic malignant syndrome. Have a significant risk of suicidal or violent behavior. Have a positive human immunodeficiency virus antibody, (HIV-Ab), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) antibody result at screening or have a history of positive result. Have received an investigational drug within 30 days before screening or plan to use an investigational drug (other than NBI-98854) during the study. Have an allergy, hypersensitivity, or intolerance to tetrabenazine. Had a blood loss greater than or equal to 500 mL or donated blood within 56 days of study start. Have had previous exposure with NBI-98854.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NBI-98854 followed by NBI-98854 with ketoconazole<br>50 mg NBI-98854 on Study Days 1 and 6 and 200 mg ketoconazole twice daily on Study Days 5 through 9. | Drug: NBI-98854 50 mg capsule once daily<br> <br> Drug: Ketoconazole 400 mg (200 mg twice daily)<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of plasma concentrations of NBI-98854 and metabolites following administration of NBI-98854 alone |  | 45 minutes prior to NBI-98854 dosing, and at 15, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 8, 12, 18, 24, 48, 72 and 96 hours postdose | 
| Evaluation of plasma concentrations of NBI-98854 and metabolites following administration of NBI-98854 concomitantly with ketoconazole |  | at 45 minutes prior to NBI-98854 dosing, and at 15, 30, 45 minutes, and 1, 1.5, 2, 3, 4, 8, 12, 18, 24, 48, 72 and 96 hours postdose | 
| Number of Participants with Adverse Events following dosing with NBI-98854 |  | Up to 31 days |