Fed Bioequivalence Study of Zolpidem Tartrate Tablets and Ambien® Tablets

Phase 1

Completed

Conditions: Healthy
Therapeutic Equivalency

Interventions: Drug: Zolpidem Tartrate 10 mg tablet (Ambien®)
Drug: Zolpidem Tartrate 10 mg tablet

Registration Number: NCT00658541

Lead Sponsor: Mutual Pharmaceutical Company, Inc.

Brief Summary: The purpose of this study is to compare the bioequivalence of a test formulation of zolpidem tartrate tablets to an equivalent oral dose of the commercially available Ambien® (zolpidem tartrate tablets)in adult subjects under fed conditions.

Detailed Description: The purpose of this study is to compare the bioequivalence of a test formulation of zolpidem tartrate tablets to an equivalent oral dose of the commercially available Ambien® (zolpidem tartrate tablets)in adult subjects under fed conditions.

Thirty-eight healthy, non-smoking, non-obese male and female volunteers at least 18 years of age will be randomly assigned in a crossover fashion to receive each of two zolpidem tartrate dosing regimens in sequence with a 7 day washout period between dosing periods. On the morning of Day 1, following an overnight fast of at least 10 hours and a standardized, high fat breakfast, subjects will receive either a single oral dose of the test formulation, zolpidem tartrate (1 x 10 mg tablet) or a single oral dose of the reference formulation, Ambien® (1 x 10 mg tablet). After a 7 day washout period, on the morning of Day 8 following an overnight fast of at least 10 hours and a standardized, high fat breakfast, subjects will receive the alternate regimen. Blood samples will be drawn from all participants before dosing and for 12 hours post dose at times sufficient to adequately define the pharmacokinetics of zolpidem tartrate. A further goal of this study is to evaluate the safety and tolerability of this regimen in healthy volunteers. Subjects will be monitored throughout the confinement portion of the study for adverse reactions to the study drugs and/or procedures. Blood pressure and pulse rate will be obtained prior to dosing and at 0.5, 1, 2, 4 and 12 hours post-dose. All adverse events whether elicited by query, spontaneously reported or observed by clinic staff will be evaluated by the investigator and reported in the subject's case report form.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 38

Inclusion Criteria

Sex: Male or Female; similar proportions of each preferred
Age: At least 18 years
Weight: must be 15% of ideal weight for height and frame
Subjects must be in good health and physical condition as determined by medical history
Subjects must read and sign the Consent Form

Exclusion Criteria

history of treatment for alcoholism, substance abuse, or drug abuse within past 24 months
history of malignancy, stroke, diabetes, cardiac, renal or liver disease
history of GERD, malabsorption syndrome, colon cancer, or chronic colitis, including Crohn's disease
history of treatment for asthma within the past five (5) years
history of mental depression, pulmonary disease, sleep apnea
females who are pregnant or lactating
history of hypersensitivity to zolpidem tartrate, or any hypnotic or sedative
conditions upon screening which might contraindicate or require that caution be used in the administration of zolpidem tartrate, including sitting systolic blood pressure below 90 mm Hg, or diastolic pressure below 50 mm Hg; heart rate less than 50 beats per minute after a 5-minute rest in a seated position
inability to read and/or sign the consent form
treatment with any other investigation drug during the four (4) weeks prior to the initial dosing for this study
subjects who have donated blood within four (4) weeks prior to the initial dosing for this study
subjects who smoke or use tobacco products or are currently using nicotine products (patches, gums, etc.) Three (3) months abstinence is required.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Zolpidem Tartrate (Ambien®) 10 mg Tablets	Zolpidem Tartrate 10 mg tablet (Ambien®)	A single dose of Ambien® 10 mg administered following an overnight fast of at least 10 hours and a standardized, high fat breakfast.
Zolpidem Tartrate 10 mg Tablets	Zolpidem Tartrate 10 mg tablet	A single dose of zolpidem tartrate 10 mg administered following an overnight fast of at least 10 hours and a standardized, high fat breakfast.

Primary Outcome Measures

Name	Time	Method
Maximum Plasma Concentration (Cmax) for Zolpidem Tartrate	serial pharmacokinetic blood samples drawn prior to dosing (hour 0), and then at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 4, 5, 6, 8, 10, and 12 hours after dose administration	The maximum or peak concentration that zolpidem tartrate reaches in the plasma.
Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] for Zolpidem Tartrate	serial pharmacokinetic blood samples drawn prior to dosing (hour 0), and then at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 4, 5, 6, 8, 10, and 12 hours after dose administration	The area under the plasma concentration versus time curve, from time 0 to the time of the last measurable zolpidem tartrate concentration (t), as calculated by the linear trapezoidal rule.
Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]for Zolpidem Tartrate	serial pharmacokinetic blood samples drawn prior to dosing (hour 0), then 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 4, 5, 6, 8, 10, and 12 hours after dose administration	The area under the zolpidem tartrate plasma concentration versus time curve from time 0 to infinity. AUC(0-∞) was calculated as the sum of AUC(0-t) plus the ratio of the last measurable plasma concentration to the elimination rate constant