Healthy
Conditions
Keywords
Bioequivalence, Healthy Subjects, Healthy, Normal Subjects
Brief summary
The primary object of this study was to evaluate the relative bioavailability of the test formulation of metronidazole vaginal gel with the already marketed reference formulation MetroGel-Vaginal Gel® in healthy adult female subjects.
Detailed description
Criteria for Evaluation: FDA Bioequivalence Criteria Statistical Methods: FDA Bioequivalence Statistical Methods
Interventions
DRUGMetronidazole
Vaginal Gel, 0.75%
Sponsors
Teva Pharmaceuticals USA
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Females, 18 years of age or older. * Good health as determined by lack of clinically significant abnormalities in health assessments performed at screening. * Signed informed consent form, which meets all criteria of current FDA regulations. * If female and of child bearing potential prepared to abstain from sexual intercourse or use a reliable method of contraception during the study (e.g. condom, IUD, oral or implanted hormonal contraceptives). * Weight within + 25% from normal for height and weight for body frame as described in Novum Standard Operating Procedures adapted from the MetLife® Height and Weight Tablets, Copyright© 1993.
Exclusion criteria
* Females who are pregnant, lactating, or likely to become pregnant during the study. * History of allergy or sensitivity to metronidazole, or history of any drug hypersensitivity or intolerance which, in the opinion of the Investigator, would compromise the safety of the subject or the study. * Significant history or current evidence of chronic infectious disease, system disorder or organ disorder. * History of psychiatric disorders occurring within the last two years that required hospitalization or medication. * Presence of a medical condition requiring regular treatment with prescription drugs (other than contraceptives or hormonal replacement therapy). * Use of pharmacologic agents known to significantly induce or inhibit drug-metabolizing enzymes within 30 days prior to dosing. * Receipt of any drug as part of a research study within 30 days prior to dosing. * Drug or alcohol addiction requiring treatment in the past 12 months. * Donation or significant loss of whole blood (480 mL or more) within 30 days or plasma within 14 days prior to dosing. * Positive test for HIV, Hepatitis B surface antigen or Hepatitis C antibody. * Positive test results for drugs of abuse at screening. * Evidence of vulvovaginitis or cervicitis (e.g. Bacterial vaginosis, vaginal candidiasis, Trichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhea, or history of Herpes simplex or human papillomavirus). * Vulvar or vaginal conditions that may affect absorption of the drug. * Clinically significant abnormal findings on PAP smear within previous 12 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax (Maximum Observed Concentration of Drug Substance in Plasma) | Blood samples collected over a 60 hour period. | Bioequivalence based on Cmax. |
| AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | Blood samples collected over a 60 hour period. | Bioequivalence based on AUC0-t. |
| AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) | Blood samples collected over a 60 hour period. | Bioequivalence based on AUC0-inf. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Test (Metronidazole) First 0.75% Metronidazole Vaginal Gel test product dosed in first period followed by 0.75% MetroGel-Vaginal® reference product dosed in the second period. | 19 |
| Reference (MetroGel-Vaginal®) First 0.75% MetroGel-Vaginal® reference product dosed in first period followed by 0.75% Metronidazole Vaginal Gel test product dosed in the second period. | 19 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Second Intervention | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Test (Metronidazole) First | Reference (MetroGel-Vaginal®) First | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants | 19 Participants | 38 Participants |
| Race/Ethnicity, Customized Black | 4 participants | 8 participants | 12 participants |
| Race/Ethnicity, Customized Caucasian | 13 participants | 11 participants | 24 participants |
| Race/Ethnicity, Customized More Than One | 2 participants | 0 participants | 2 participants |
| Region of Enrollment United States | 19 participants | 19 participants | 38 participants |
| Sex: Female, Male Female | 19 Participants | 19 Participants | 38 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 38 | 16 / 38 |
| serious Total, serious adverse events | 0 / 38 | 0 / 38 |
Outcome results
Primary
AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity)
Bioequivalence based on AUC0-inf.
Time frame: Blood samples collected over a 60 hour period.
Population: All participants that completed the study had their samples analyzed. One subject had very low plasma metronidazole levels for Period I samples, therefore the data from this subject was dropped from the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test (Metronidazole) | AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) | 5989.237 ng*h/mL | Standard Deviation 1737.791 |
| Reference (MetroGel-Vaginal®) | AUC0-inf (Area Under the Concentration-time Curve From Time Zero to Infinity) | 5693.259 ng*h/mL | Standard Deviation 1735.116 |
90% CI: [97.6, 115]
Primary
AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration)
Bioequivalence based on AUC0-t.
Time frame: Blood samples collected over a 60 hour period.
Population: All participants that completed the study had their samples analyzed. One subject had very low plasma metronidazole levels for Period I samples, therefore the data from this subject was dropped from the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test (Metronidazole) | AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 5921.046 ng*h/mL | Standard Deviation 1713.316 |
| Reference (MetroGel-Vaginal®) | AUC0-t (Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration) | 5593.855 ng*h/mL | Standard Deviation 1683.155 |
90% CI: [98.2, 115]
Primary
Cmax (Maximum Observed Concentration of Drug Substance in Plasma)
Bioequivalence based on Cmax.
Time frame: Blood samples collected over a 60 hour period.
Population: All participants that completed the study had their samples analyzed. One subject had very low plasma metronidazole levels for Period I samples, therefore the data from this subject was dropped from the statistical analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Test (Metronidazole) | Cmax (Maximum Observed Concentration of Drug Substance in Plasma) | 281.111 ng/mL | Standard Deviation 72.222 |
| Reference (MetroGel-Vaginal®) | Cmax (Maximum Observed Concentration of Drug Substance in Plasma) | 257.194 ng/mL | Standard Deviation 71.228 |
90% CI: [103, 117]