Healthy
Conditions
Keywords
equivalency, Therapeutic equivalency
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 reference drug product Ambien® (zolpidem tartrate tablets) in adult subjects under fasted 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 reference drug product Ambien® (zolpidem tartrate tablets) in adult subjects under fasted 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, after an overnight fast of at least 10 hours, 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 after an overnight fast, 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.
Interventions
10 mg tablet administered after an overnight fast of at least 10 hours
10 mg tablet administered after an overnight fast of at least 10 hours
Sponsors
Mutual Pharmaceutical Company, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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, or other serious illness. * 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. * History of pulmonary disease. * History of sleep apnea. * Females who are pregnant or lactating. * History of hypersensitivity to zolpidem tartrate, or any hypnotic or sedative. * Treatment with any other investigational drug during the four weeks prior to the initial dosing of the study. * Donation of blood within four weeks prior to the initial dosing of the study * Smokers or subjects who use tobacco/nicotine products. Three months abstinence is required.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Zolpidem Tartrate 10 mg Tablets and Ambien® 10 mg Tablets All subjects received each of the two study regimens in a randomly assigned sequence of dosing periods. On the mornings of Day 1 and Day 8, each subject received one tablet of either zolpidem tartrate 10 mg or Ambien® 10 mg following an overnight fast of at least 10 hours. | 38 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Second Intervention | Adverse Event | 1 | 0 |
| Washout Period of 7 Days | Adverse Event | 1 | 2 |
| Washout Period of 7 Days | Withdrawal by Subject | 1 | 2 |
Baseline characteristics
| Characteristic | Zolpidem Tartrate 10 mg Tablets and Ambien® 10 mg Tablets |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 38 Participants |
| Age Continuous | 28.92 years STANDARD_DEVIATION 8.64 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 33 Participants |
| Region of Enrollment United States | 38 participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 34 | 14 / 36 |
| serious Total, serious adverse events | 0 / 34 | 0 / 36 |
Outcome results
Primary
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.
Time frame: 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
Population: Plasma concentration data for 31 of 38 participants were used in the statistical analysis. Six subjects dropped from study period I and one subject dropped from study period II.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Zolpidem Tartrate 10 mg Tablets | Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]for Zolpidem Tartrate | 723.14 ng-hr/mL | Standard Deviation 327.83 |
| Ambien® 10 mg Tablets | Area Under the Concentration Versus Time Curve From Time 0 Extrapolated to Infinity [AUC(0-∞)]for Zolpidem Tartrate | 739.63 ng-hr/mL | Standard Deviation 351.51 |
Primary
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.
Time frame: 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
Population: Plasma concentration data for 31 of 38 participants were used in the statistical analysis. Six subjects dropped from study period I and one subject dropped from study period II.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Zolpidem Tartrate 10 mg Tablets | Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] for Zolpidem Tartrate | 682.17 ng-hr/mL | Standard Deviation 285.78 |
| Ambien® 10 mg Tablets | Area Under the Concentration Versus Time Curve From Time 0 to Time t [AUC(0-t)] for Zolpidem Tartrate | 692.47 ng-hr/mL | Standard Deviation 290.89 |
Primary
Maximum Plasma Concentration (Cmax) for Zolpidem Tartrate
The maximum or peak concentration that zolpidem tartrate reaches in the plasma.
Time frame: 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
Population: Plasma concentration data for 31 of 38 participants were used in the statistical analysis. Six subjects dropped from study period I and one subject dropped from study period II.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Zolpidem Tartrate 10 mg Tablets | Maximum Plasma Concentration (Cmax) for Zolpidem Tartrate | 191.94 ng/mL | Standard Deviation 74.77 |
| Ambien® 10 mg Tablets | Maximum Plasma Concentration (Cmax) for Zolpidem Tartrate | 193.43 ng/mL | Standard Deviation 59.95 |