Fed Bioequivalence Study of Zolpidem Tartrate Tablets and Ambien® Tablets

Study Overview
=================
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.

Official Title
-----------------
A Randomized, Two-way Crossover, Single-dose, Open-label Study to Evaluate the Relative Bioequivalence of a Test Tablet Formulation of Zolpidem Tartrate 10mg, Compared to an Equivalent Dose of Ambien® in Fed, Healthy, Adult Subjects

Conditions
-----------------
Healthy, Therapeutic Equivalency

Intervention / Treatment
-----------------
* Drug: Zolpidem Tartrate 10 mg tablet
* Drug: Zolpidem Tartrate 10 mg tablet (Ambien®)


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zolpidem Tartrate 10 mg Tablets<br>A single dose of zolpidem tartrate 10 mg administered following an overnight fast of at least 10 hours and a standardized, high fat breakfast. | Drug: Zolpidem Tartrate 10 mg tablet<br>* 10 mg tablet administered following an overnight fast of at least 10 hours and a standardized, high fat breakfast.<br>|
| Active Comparator: Zolpidem Tartrate (Ambien®) 10 mg Tablets<br>A single dose of Ambien® 10 mg administered following an overnight fast of at least 10 hours and a standardized, high fat breakfast. | Drug: Zolpidem Tartrate 10 mg tablet (Ambien®)<br>* 10 mg tablet administered following an overnight fast of at least 10 hours and a standardized, high fat breakfast.<br>* Other names: Ambien®;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration (Cmax) for Zolpidem Tartrate | The maximum or peak concentration that zolpidem tartrate reaches in the plasma. | 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 | 
| Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] for Zolpidem Tartrate | 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. | 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 | 
| Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]for Zolpidem Tartrate | 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 | 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 |