Antifungal Agents
Conditions
Keywords
Griseofulvin, Bioequivalence, Dose proportionality, Dermatophytosis
Brief summary
Griseofulvin is an antifungal agent used in treatment of Dermatophytosis caused by Microsporum spp. (species), Trichophyton spp., Epidermophyton spp., where topical therapy is considered inappropriate or has failed. Approved dose of Griseofulvin in Adults (greater than or equal to 50 kg) in India is 500 to 1,000 mg daily, but not less than 10 mg/kg bodyweight daily. As per the World health organization (WHO) guidance, Griseofulvin belongs to Biopharmaceutical Classification System (BCS) Class 2 (low solubility-high permeability). A Bioequivalence (BE) study will be conducted in India to estimate in vivo behavior (Pharmacokinetic characteristics) of Griseofulvin 500 tablets and dose proportionality study for Griseofulvin 250 mg and 500 mg tablets. This is an open label, randomized, balanced, three treatment period, three sequence, single dose, crossover study that will evaluate the bioequivalence of Griseofulvin tablets 500 mg test product (T1) versus Griseofulvin tablets 500 mg reference product (R) as well as dose proportionality of Griseofulvin tablets 250 mg test product (T2) with Griseofulvin tablets 500 mg T1 in healthy, adult participants under fed conditions. Eligible participants enrolled will be randomized to either of the three treatment sequence periods, T1T2R, T2RT1 or RT1T2 according to 1:1:1 ratio. The total duration of clinical phase will be approximately 20 days from Day-1 to Day 19 including a washout period of at least 7 days (not more than 14 days) for each treatment period. A total of 36 healthy, adult participants will be enrolled in this study and the above mentioned doses of Griseofulvin will be administered under fed conditions. Participants will be followed up 5 days after last dosing.
Interventions
DRUGGriseofulvin 500 mg
Griseofulvin 500 mg will be administered as an oral tablet once in each treatment period under fed condition.
DRUGGriseofulvin 250 mg
Griseofulvin 250 mg will be administered as an oral tablet once in each treatment period under fed condition.
DRUGReference Griseofulvin 500 mg
Reference Griseofulvin 500 mg will be administered as an oral tablet once in each treatment period under fed condition.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The whole study will be divided into three treatment periods. For each treatment period, eligible participants will be randomized to either T1T2R, T2RT1 or RT1T2 treatment sequence according to 1:1:1 ratio
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Participant must be 18 to 45 years of age inclusive, at the time of signing the informed consent. * Participants who are healthy as determined by the investigator or medically qualified designee on a medical evaluation including medical baseline history, physical examination and vital sign examination (blood pressure, pulse rate, respiration rate and body temperature). * Participants with clinically acceptable findings as determined by hematology, biochemistry, urinalysis, 12 lead electrocardiogram (ECG). * Participant's willingness to follow the protocol requirements especially abstaining from xanthine containing food or beverages (chocolates, tea, coffee or cola drinks) or grapefruit or grapefruit juice, any alcoholic products, the use of cigarettes and the use of tobacco products from 48 hours before the start of dosing until after collection of the final pharmacokinetic sample and adherence to food, fluid and posture restrictions. * Participants with no history of significant alcoholism (Volunteers who do not have habit of heavy drinking which is defined as regular intake of more than 2 units of alcohol per day for male and 1 unit for female \[I unit= 150 mL of wine or 360 mL of beer or 45 mL of 40 percent (%) of alcohol\]). * Participants with no history of drug abuse (benzodiazepines and barbiturates) for the last one month and other illegal drugs for the last 6 months. * Participants who are non-smokers and ex-smokers will be included. Ex-smokers are someone who completely stopped smoking for at least 3 months. * Body mass index (BMI) within the range 18.5-30 kilogram per meter square (kg/m\^2) (inclusive) and weight \>= 50 kg. * Healthy Male and non-pregnant female: Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. * Male participants are eligible to participate if they agree to the following during the treatment period and for at least six months after the last dose of study treatment. • Refrain from donating sperm as well as agree to use contraception/barrier as detailed below 1. Agree to use a male condom and should also be advised for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential who is not currently pregnant. 2. Agree to use male condom when engaging in any activity that allows for passage of ejaculate to another person. * A female participant is eligible to participate if she is not pregnant and intending to become pregnant or breastfeeding, and at least one of the following conditions applies: * Is not a woman of childbearing potential (WOCBP) OR * Is a WOCBP and using a contraceptive method that is highly effective, with a failure rate of \<1% during the treatment period and for at least 1 month after the last dose of study treatment. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study treatment. * A WOCBP must have a negative highly sensitive pregnancy test (serum as required by local regulations) within 1 day before each dose of study treatment (The participant must be excluded from participation if the serum pregnancy result is positive). b) Additional requirements for pregnancy testing during and after study treatment. c) The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. * Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
Exclusion criteria
* Known history of hypersensitivity to Griseofulvin. * Participants who have taken prescription medications or over-the-counter products (including vitamins, minerals and/or herbal supplements) within 14 days prior to administration of Investigational Medicinal Product (IMP). * Any medical or surgical conditions, which might significantly interfere with the functioning of gastrointestinal tract, blood-forming organs, etc. * History of cardiovascular, renal, hepatic, ophthalmic, pulmonary, neurological, metabolic, hematological, gastrointestinal, endocrine, immunological or psychiatric diseases. * History of malignancy (including skin cancers) or other serious diseases. * History of porphyria. * Known history of Systemic lupus erythematosus (SLE) in the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration (Cmax) for Griseofulvin | Pre-dose (within 1 hour prior to dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 10, 12, 24, 48, 72 and 96 hours post-dose in each period | Blood samples were collected to measure Cmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. For Griseofulvin 250 mg (T2), dose-normalized Cmax (observed value multiplied by 2) is reported. Adjusted geometric mean and standard error have been presented for all treatments. Adjusted geometric mean is the antilog (exponential) of the least squares mean of the log-transformed data. Statistical analysis of pharmacokinetic parameters was done using mixed model for evaluation of bioquivalence. Point estimate and 90% confidence interval for the ratio of geometric least square mean of the test Griseofulvin 500 mg (T1) to the reference Griseofulvin 500 mg (R) were calculated for Cmax to assess bioequivalence. |
| Area Under Plasma Concentration-time Curve (AUC) From Zero Hours to Time of Last Quantifiable Concentration (AUC[0-t]) for Griseofulvin | Pre-dose (within 1 hour prior to dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 10, 12, 24, 48, 72 and 96 hours post-dose in each period | Blood samples were collected to measure AUC(0-t) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. For Griseofulvin 250 mg (T2), dose-normalized AUC(0-t) (observed value multiplied by 2) is reported. Adjusted geometric mean and standard error have been presented for all treatments. Adjusted geometric mean is the antilog (exponential) of the least squares mean of the log-transformed data. Statistical analysis of pharmacokinetic parameters was done using mixed model for evaluation of bioquivalence. Point estimate and 90% confidence interval for the ratio of geometric least square mean of the test Griseofulvin 500 mg (T1) to the reference Griseofulvin 500 mg (R) were calculated for AUC(0-t) to assess bioequivalence. |
| AUC From Time Zero Extrapolated to Infinity (AUC[0-inf]) for Griseofulvin | Pre-dose (within 1 hour prior to dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 10, 12, 24, 48, 72 and 96 hours post-dose in each period | Blood samples were collected to measure AUC(0-inf) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. For Griseofulvin 250 mg (T2), dose-normalized AUC(0-inf) (observed value multiplied by 2) is reported. Adjusted geometric mean and standard error have been presented for all treatments. Adjusted geometric mean is the antilog (exponential) of the least squares mean of the log-transformed data. Statistical analysis of pharmacokinetic parameters was done using mixed model for evaluation of bioquivalence. Point estimate and 90% confidence interval for the ratio of geometric least square mean of the test Griseofulvin 500 mg (T1) to the reference Griseofulvin 500 mg (R) were calculated for AUC(0-inf) to assess bioequivalence. |
| Dose Proportionality of Griseofulvin Using AUC(0-t) Following a Single Dose | Pre-dose (within 1 hour prior to dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 10, 12, 24, 48, 72 and 96 hours post-dose in each period | Blood samples were collected at indicated time-points for pharmacokinetic analysis. Pharmacokinetic parameters were measured using standard non-compartmental methods. Dose proportionality was assessed using mixed model. Slope and 90% confidence interval for the slope are presented. For Griseofulvin 250 mg (T2), dose-normalized (observed value multiplied by 2) AUC(0-t) was used during calculation of dose proportionality. |
| Dose Proportionality of Griseofulvin Using Cmax Following a Single Dose | Pre-dose (within 1 hour prior to dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 10, 12, 24, 48, 72 and 96 hours post-dose in each period | Blood samples were collected at indicated time-points for pharmacokinetic analysis. Pharmacokinetic parameters were measured using standard non-compartmental methods. Dose proportionality was assessed using mixed model. Slope and 90% confidence interval for the slope are presented. For Griseofulvin 250 mg (T2), dose-normalized (observed value multiplied by 2) Cmax was used during calculation of dose proportionality. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Positive Results in Serum Beta-human Chorionic Gonadotropin (Beta-hCG) Level (Females Participants) | Days -1, 7, 17 and 22 | Blood samples were collected at indicated time points for assessment of serum beta-hCG (serum pregnancy test) for female participants. Number of participants with positive results in serum beta-hCG levels are presented. |
| Number of Participants With Any Serious Adverse Event (SAE) and Any Non-serious Adverse Event (Non-SAE) | Up to Day 22 | An adverse event was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the medicinal product. An SAE was any untoward medical occurrence resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, congenital anomaly/birth defect or any other other important medical event that may jeopardize the participant or may require medical or surgical treatment to prevent one of the other outcomes listed before. |
| Number of Participants With Abnormal Urinalysis Dipstick Results | Up to Day 22 | Urine samples were collected to assess glucose, ketones, occult blood, protein, urobilinogen and bilirubin by dipstick method. The dipstick test gave results in a semi-quantitative manner, and results can be read as Negative, Trace, 1+, 2+ indicating proportional concentrations in the urine sample. Clinically acceptable range included 'negative' and 'trace' results. Number of participants with any abnormal urinalysis parameters are presented. |
| Number of Participants With Any Abnormality in Vital Signs | Up to Day 22 | Systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate, respiration rate and body temperature were measured in semi-supine position after 5 minutes rest. The clinically acceptable range included; SBP: 85 millimeters of mercury (mmHg) to 160 mmHg; DBP: 45 mmHg to 100 mmHg; pulse rate: 40 beats per minute to 110 beats per minute; respiration rate: 8 breaths per minute to 20 breaths per minute; body temperature: 35.5 degrees Celsius to 37.8 degrees Celsius. Number of participants with any abnormality in vital signs are presented. |
| Number of Participants With Any Abnormality in Hematology Parameters | Up to Day 22 | Blood samples were collected at indicated time points for assessment of hematology parameters. The clinically acceptable range included; hemoglobin: 12.3-18.0 grams per deciliter (g/dL) (for male) and 11.0-16.0 g/dL (for female), erythrocyte count: 4.0-7.1\*10\^12 cells per liter (for male) and 3.6-5.6\*10\^12 cells per liter (for female), hematocrit: 0.41-0.50 proportion of red blood cells in blood (Male) and 0.35-0.44 proportion of red blood cells in blood (Female), Mean Corpuscular Volume (MCV): 80-96 femtoliters, Mean Corpuscular Hemoglobin (MCH): 27.5-33.2 picogram , Mean Corpuscular Hemoglobin Concentration (MCHC): 33.4-35.5 g/dL, White Blood Cell (WBC) count: 3960-12100 cells per microliter, platelet count: 135-495\*10\^9 cells per liter, neutrophils: 36-88%, eosinophils: up to 14%, basophils: 0-2%, lymphocytes: 18-44%, monocytes: 2-10% of total cells. Number of participants with any abnormality in hematology parameters are presented. |
| Number of Participants With Any Abnormality in Clinical Chemistry Parameters | Up to Day 22 | Blood samples were collected at indicated time points for assessment of clinical chemistry parameters. The clinically acceptable range included; blood urea: Up to 55 milligrams per deciliter (mg/dL), random blood glucose: 63-140 mg/dL, blood urea nitrogen: Up to 25 mg/dL, serum creatinine: 0.6-1.3 mg/dL (Male) and 0.4-1.0 mg/dL (Female), total serum bilirubin: 0.00-1.47 mg/dL, direct serum bilirubin: 0.0-0.3 mg/dL, indirect serum bilirubin: 0.0-1.5 mg/dL, aspartate aminotransferase (AST): Up to 70 units per liter (U/L) (Male) and Up to 50 U/L (Female). Number of participants with any abnormality in clinical chemistry parameters are presented. |
| Number of Participants With Any Abnormality in Clinical Chemistry Parameter: Alanine Aminotransferase (ALT) | Days -1, 7, 17 and 22 | Blood samples were collected at indicated time points for assessment of clinical chemistry parameter. The clinically acceptable range for ALT included; Up to 7270 units per liter (U/L) (Male) and Up to 50 U/L (Female). Number of participants with any abnormality in ALT levels are presented. |
Countries
India
Participant flow
Recruitment details
This was an open label, randomized,3-treatment,3-period, single dose, crossover study. Bioequivalence between test Griseofulvin tablets (500 milligram \[mg\]) versus reference Griseofulvin tablets 500 mg and dose proportionality between test Griseofulvin tablets (250 mg and 500 mg) were evaluated in healthy adult participants under fed conditions.
Pre-assignment details
A total of 36 participants were enrolled and received study treatment. The study had 3 periods: Period 1 (Day -1 to Day 5), Period 2 (Day 7 to Day 12) and Period 3 (Day 17 to Day 22) with a washout of atleast 7 days (not more than 14 days) between two subsequent dosing days.
Participants by arm
| Arm | Count |
|---|---|
| All Treated Participants All participants received a single oral dose of Griseofulvin 500 mg tablet (T1), Griseofulvin 250 mg tablet (T2) and Griseofulvin 500 mg tablet (R) in either Period 1 or Period 2 or Period 3 as per randomization schedule. | 36 |
| Total | 36 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Period2washout(Atleast 7 Days Post-dose) | Lost to Follow-up | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | All Treated Participants |
|---|---|
| Age, Continuous | 32.08 Years STANDARD_DEVIATION 5.82 |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 36 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 36 | 0 / 36 | 0 / 36 |
| other Total, other adverse events | 0 / 36 | 0 / 36 | 1 / 36 |
| serious Total, serious adverse events | 0 / 36 | 0 / 36 | 0 / 36 |
Outcome results
Primary
Area Under Plasma Concentration-time Curve (AUC) From Zero Hours to Time of Last Quantifiable Concentration (AUC[0-t]) for Griseofulvin
Blood samples were collected to measure AUC(0-t) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. For Griseofulvin 250 mg (T2), dose-normalized AUC(0-t) (observed value multiplied by 2) is reported. Adjusted geometric mean and standard error have been presented for all treatments. Adjusted geometric mean is the antilog (exponential) of the least squares mean of the log-transformed data. Statistical analysis of pharmacokinetic parameters was done using mixed model for evaluation of bioquivalence. Point estimate and 90% confidence interval for the ratio of geometric least square mean of the test Griseofulvin 500 mg (T1) to the reference Griseofulvin 500 mg (R) were calculated for AUC(0-t) to assess bioequivalence.
Time frame: Pre-dose (within 1 hour prior to dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 10, 12, 24, 48, 72 and 96 hours post-dose in each period
Population: Bioequivalence (BE) Analysis Set Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Griseofulvin 500 mg (T1) | Area Under Plasma Concentration-time Curve (AUC) From Zero Hours to Time of Last Quantifiable Concentration (AUC[0-t]) for Griseofulvin | 54993 Hours*nanogram per milliliter | Standard Error 0.05305 |
| Griseofulvin 250 mg (T2) | Area Under Plasma Concentration-time Curve (AUC) From Zero Hours to Time of Last Quantifiable Concentration (AUC[0-t]) for Griseofulvin | 66788 Hours*nanogram per milliliter | Standard Error 0.0556 |
| Griseofulvin 500 mg (R) | Area Under Plasma Concentration-time Curve (AUC) From Zero Hours to Time of Last Quantifiable Concentration (AUC[0-t]) for Griseofulvin | 53274 Hours*nanogram per milliliter | Standard Error 0.05305 |
90% CI: [0.974, 1.094]
Primary
AUC From Time Zero Extrapolated to Infinity (AUC[0-inf]) for Griseofulvin
Blood samples were collected to measure AUC(0-inf) at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. For Griseofulvin 250 mg (T2), dose-normalized AUC(0-inf) (observed value multiplied by 2) is reported. Adjusted geometric mean and standard error have been presented for all treatments. Adjusted geometric mean is the antilog (exponential) of the least squares mean of the log-transformed data. Statistical analysis of pharmacokinetic parameters was done using mixed model for evaluation of bioquivalence. Point estimate and 90% confidence interval for the ratio of geometric least square mean of the test Griseofulvin 500 mg (T1) to the reference Griseofulvin 500 mg (R) were calculated for AUC(0-inf) to assess bioequivalence.
Time frame: Pre-dose (within 1 hour prior to dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 10, 12, 24, 48, 72 and 96 hours post-dose in each period
Population: Bioequivalence (BE) Analysis Set Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Griseofulvin 500 mg (T1) | AUC From Time Zero Extrapolated to Infinity (AUC[0-inf]) for Griseofulvin | 56746 Hours*nanogram per milliliter | Standard Error 0.0546 |
| Griseofulvin 250 mg (T2) | AUC From Time Zero Extrapolated to Infinity (AUC[0-inf]) for Griseofulvin | 69564 Hours*nanogram per milliliter | Standard Error 0.0563 |
| Griseofulvin 500 mg (R) | AUC From Time Zero Extrapolated to Infinity (AUC[0-inf]) for Griseofulvin | 55100 Hours*nanogram per milliliter | Standard Error 0.0546 |
90% CI: [0.971, 1.093]
Primary
Dose Proportionality of Griseofulvin Using AUC(0-t) Following a Single Dose
Blood samples were collected at indicated time-points for pharmacokinetic analysis. Pharmacokinetic parameters were measured using standard non-compartmental methods. Dose proportionality was assessed using mixed model. Slope and 90% confidence interval for the slope are presented. For Griseofulvin 250 mg (T2), dose-normalized (observed value multiplied by 2) AUC(0-t) was used during calculation of dose proportionality.
Time frame: Pre-dose (within 1 hour prior to dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 10, 12, 24, 48, 72 and 96 hours post-dose in each period
Population: Dose Proportionality Analysis Set Population comprised of participants completing at least 2 periods with 500 mg test (T1) and 250 mg test (T2) treatments of the study. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Griseofulvin 500 mg (T1) | Dose Proportionality of Griseofulvin Using AUC(0-t) Following a Single Dose | 1.214 Slope of log dose |
Primary
Dose Proportionality of Griseofulvin Using Cmax Following a Single Dose
Blood samples were collected at indicated time-points for pharmacokinetic analysis. Pharmacokinetic parameters were measured using standard non-compartmental methods. Dose proportionality was assessed using mixed model. Slope and 90% confidence interval for the slope are presented. For Griseofulvin 250 mg (T2), dose-normalized (observed value multiplied by 2) Cmax was used during calculation of dose proportionality.
Time frame: Pre-dose (within 1 hour prior to dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 10, 12, 24, 48, 72 and 96 hours post-dose in each period
Population: Dose Proportionality Analysis Set Population comprised of participants completing at least 2 periods with 500 mg test (T1) and 250 mg test (T2) treatments of the study. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Griseofulvin 500 mg (T1) | Dose Proportionality of Griseofulvin Using Cmax Following a Single Dose | 1.290 Slope of log dose |
Primary
Maximum Plasma Concentration (Cmax) for Griseofulvin
Blood samples were collected to measure Cmax at indicated time-points. Pharmacokinetic parameters were measured using standard non-compartmental methods. For Griseofulvin 250 mg (T2), dose-normalized Cmax (observed value multiplied by 2) is reported. Adjusted geometric mean and standard error have been presented for all treatments. Adjusted geometric mean is the antilog (exponential) of the least squares mean of the log-transformed data. Statistical analysis of pharmacokinetic parameters was done using mixed model for evaluation of bioquivalence. Point estimate and 90% confidence interval for the ratio of geometric least square mean of the test Griseofulvin 500 mg (T1) to the reference Griseofulvin 500 mg (R) were calculated for Cmax to assess bioequivalence.
Time frame: Pre-dose (within 1 hour prior to dosing) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 10, 12, 24, 48, 72 and 96 hours post-dose in each period
Population: Bioequivalence (BE) Analysis Set Population comprised of participants completing at least 2 periods with 500 mg test and 500 mg reference treatments of the study. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Griseofulvin 500 mg (T1) | Maximum Plasma Concentration (Cmax) for Griseofulvin | 2229 Nanograms per milliliter | Standard Error 0.03262 |
| Griseofulvin 250 mg (T2) | Maximum Plasma Concentration (Cmax) for Griseofulvin | 2877 Nanograms per milliliter | Standard Error 0.03457 |
| Griseofulvin 500 mg (R) | Maximum Plasma Concentration (Cmax) for Griseofulvin | 1927 Nanograms per milliliter | Standard Error 0.03262 |
90% CI: [1.103, 1.213]
Secondary
Number of Participants With Abnormal Urinalysis Dipstick Results
Urine samples were collected to assess glucose, ketones, occult blood, protein, urobilinogen and bilirubin by dipstick method. The dipstick test gave results in a semi-quantitative manner, and results can be read as Negative, Trace, 1+, 2+ indicating proportional concentrations in the urine sample. Clinically acceptable range included 'negative' and 'trace' results. Number of participants with any abnormal urinalysis parameters are presented.
Time frame: Up to Day 22
Population: Safety Analysis Set Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Griseofulvin 500 mg (T1) | Number of Participants With Abnormal Urinalysis Dipstick Results | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Abnormal Urinalysis Dipstick Results | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Abnormal Urinalysis Dipstick Results | 0 Participants |
Secondary
Number of Participants With Any Abnormality in Clinical Chemistry Parameter: Alanine Aminotransferase (ALT)
Blood samples were collected at indicated time points for assessment of clinical chemistry parameter. The clinically acceptable range for ALT included; Up to 7270 units per liter (U/L) (Male) and Up to 50 U/L (Female). Number of participants with any abnormality in ALT levels are presented.
Time frame: Days -1, 7, 17 and 22
Population: Safety Analysis Set Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Griseofulvin 500 mg (T1) | Number of Participants With Any Abnormality in Clinical Chemistry Parameter: Alanine Aminotransferase (ALT) | Day -1 | 0 Participants |
| Griseofulvin 500 mg (T1) | Number of Participants With Any Abnormality in Clinical Chemistry Parameter: Alanine Aminotransferase (ALT) | Day 7 | 0 Participants |
| Griseofulvin 500 mg (T1) | Number of Participants With Any Abnormality in Clinical Chemistry Parameter: Alanine Aminotransferase (ALT) | Day 17 | 0 Participants |
| Griseofulvin 500 mg (T1) | Number of Participants With Any Abnormality in Clinical Chemistry Parameter: Alanine Aminotransferase (ALT) | Day 22 | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Any Abnormality in Clinical Chemistry Parameter: Alanine Aminotransferase (ALT) | Day 22 | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Any Abnormality in Clinical Chemistry Parameter: Alanine Aminotransferase (ALT) | Day -1 | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Any Abnormality in Clinical Chemistry Parameter: Alanine Aminotransferase (ALT) | Day 17 | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Any Abnormality in Clinical Chemistry Parameter: Alanine Aminotransferase (ALT) | Day 7 | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Any Abnormality in Clinical Chemistry Parameter: Alanine Aminotransferase (ALT) | Day 22 | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Any Abnormality in Clinical Chemistry Parameter: Alanine Aminotransferase (ALT) | Day 7 | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Any Abnormality in Clinical Chemistry Parameter: Alanine Aminotransferase (ALT) | Day 17 | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Any Abnormality in Clinical Chemistry Parameter: Alanine Aminotransferase (ALT) | Day -1 | 0 Participants |
Secondary
Number of Participants With Any Abnormality in Clinical Chemistry Parameters
Blood samples were collected at indicated time points for assessment of clinical chemistry parameters. The clinically acceptable range included; blood urea: Up to 55 milligrams per deciliter (mg/dL), random blood glucose: 63-140 mg/dL, blood urea nitrogen: Up to 25 mg/dL, serum creatinine: 0.6-1.3 mg/dL (Male) and 0.4-1.0 mg/dL (Female), total serum bilirubin: 0.00-1.47 mg/dL, direct serum bilirubin: 0.0-0.3 mg/dL, indirect serum bilirubin: 0.0-1.5 mg/dL, aspartate aminotransferase (AST): Up to 70 units per liter (U/L) (Male) and Up to 50 U/L (Female). Number of participants with any abnormality in clinical chemistry parameters are presented.
Time frame: Up to Day 22
Population: Safety Analysis Set Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Griseofulvin 500 mg (T1) | Number of Participants With Any Abnormality in Clinical Chemistry Parameters | Blood urea | 0 Participants |
| Griseofulvin 500 mg (T1) | Number of Participants With Any Abnormality in Clinical Chemistry Parameters | Random blood glucose | 0 Participants |
| Griseofulvin 500 mg (T1) | Number of Participants With Any Abnormality in Clinical Chemistry Parameters | Blood urea nitrogen | 0 Participants |
| Griseofulvin 500 mg (T1) | Number of Participants With Any Abnormality in Clinical Chemistry Parameters | Serum creatinine | 0 Participants |
| Griseofulvin 500 mg (T1) | Number of Participants With Any Abnormality in Clinical Chemistry Parameters | Total serum bilirubin | 0 Participants |
| Griseofulvin 500 mg (T1) | Number of Participants With Any Abnormality in Clinical Chemistry Parameters | Direct serum bilirubin | 0 Participants |
| Griseofulvin 500 mg (T1) | Number of Participants With Any Abnormality in Clinical Chemistry Parameters | Indirect serum bilirubin | 0 Participants |
| Griseofulvin 500 mg (T1) | Number of Participants With Any Abnormality in Clinical Chemistry Parameters | AST | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Any Abnormality in Clinical Chemistry Parameters | Blood urea nitrogen | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Any Abnormality in Clinical Chemistry Parameters | Indirect serum bilirubin | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Any Abnormality in Clinical Chemistry Parameters | Serum creatinine | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Any Abnormality in Clinical Chemistry Parameters | Total serum bilirubin | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Any Abnormality in Clinical Chemistry Parameters | Direct serum bilirubin | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Any Abnormality in Clinical Chemistry Parameters | Blood urea | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Any Abnormality in Clinical Chemistry Parameters | Random blood glucose | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Any Abnormality in Clinical Chemistry Parameters | AST | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Any Abnormality in Clinical Chemistry Parameters | Blood urea nitrogen | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Any Abnormality in Clinical Chemistry Parameters | Random blood glucose | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Any Abnormality in Clinical Chemistry Parameters | Blood urea | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Any Abnormality in Clinical Chemistry Parameters | Serum creatinine | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Any Abnormality in Clinical Chemistry Parameters | Indirect serum bilirubin | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Any Abnormality in Clinical Chemistry Parameters | Direct serum bilirubin | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Any Abnormality in Clinical Chemistry Parameters | Total serum bilirubin | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Any Abnormality in Clinical Chemistry Parameters | AST | 0 Participants |
Secondary
Number of Participants With Any Abnormality in Hematology Parameters
Blood samples were collected at indicated time points for assessment of hematology parameters. The clinically acceptable range included; hemoglobin: 12.3-18.0 grams per deciliter (g/dL) (for male) and 11.0-16.0 g/dL (for female), erythrocyte count: 4.0-7.1\*10\^12 cells per liter (for male) and 3.6-5.6\*10\^12 cells per liter (for female), hematocrit: 0.41-0.50 proportion of red blood cells in blood (Male) and 0.35-0.44 proportion of red blood cells in blood (Female), Mean Corpuscular Volume (MCV): 80-96 femtoliters, Mean Corpuscular Hemoglobin (MCH): 27.5-33.2 picogram , Mean Corpuscular Hemoglobin Concentration (MCHC): 33.4-35.5 g/dL, White Blood Cell (WBC) count: 3960-12100 cells per microliter, platelet count: 135-495\*10\^9 cells per liter, neutrophils: 36-88%, eosinophils: up to 14%, basophils: 0-2%, lymphocytes: 18-44%, monocytes: 2-10% of total cells. Number of participants with any abnormality in hematology parameters are presented.
Time frame: Up to Day 22
Population: Safety Analysis Set Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Griseofulvin 500 mg (T1) | Number of Participants With Any Abnormality in Hematology Parameters | Monocytes count | 0 Participants |
| Griseofulvin 500 mg (T1) | Number of Participants With Any Abnormality in Hematology Parameters | Eosinophils count | 0 Participants |
| Griseofulvin 500 mg (T1) | Number of Participants With Any Abnormality in Hematology Parameters | MCHC | 0 Participants |
| Griseofulvin 500 mg (T1) | Number of Participants With Any Abnormality in Hematology Parameters | Hematocrit | 0 Participants |
| Griseofulvin 500 mg (T1) | Number of Participants With Any Abnormality in Hematology Parameters | Neutrophils count | 0 Participants |
| Griseofulvin 500 mg (T1) | Number of Participants With Any Abnormality in Hematology Parameters | WBC count | 0 Participants |
| Griseofulvin 500 mg (T1) | Number of Participants With Any Abnormality in Hematology Parameters | Hemoglobin | 0 Participants |
| Griseofulvin 500 mg (T1) | Number of Participants With Any Abnormality in Hematology Parameters | Erythrocyte count | 0 Participants |
| Griseofulvin 500 mg (T1) | Number of Participants With Any Abnormality in Hematology Parameters | Lymphocytes count | 0 Participants |
| Griseofulvin 500 mg (T1) | Number of Participants With Any Abnormality in Hematology Parameters | MCV | 0 Participants |
| Griseofulvin 500 mg (T1) | Number of Participants With Any Abnormality in Hematology Parameters | Platelet count | 0 Participants |
| Griseofulvin 500 mg (T1) | Number of Participants With Any Abnormality in Hematology Parameters | Basophils count | 0 Participants |
| Griseofulvin 500 mg (T1) | Number of Participants With Any Abnormality in Hematology Parameters | MCH | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Any Abnormality in Hematology Parameters | WBC count | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Any Abnormality in Hematology Parameters | Hemoglobin | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Any Abnormality in Hematology Parameters | Erythrocyte count | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Any Abnormality in Hematology Parameters | Hematocrit | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Any Abnormality in Hematology Parameters | MCV | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Any Abnormality in Hematology Parameters | MCH | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Any Abnormality in Hematology Parameters | MCHC | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Any Abnormality in Hematology Parameters | Neutrophils count | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Any Abnormality in Hematology Parameters | Eosinophils count | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Any Abnormality in Hematology Parameters | Basophils count | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Any Abnormality in Hematology Parameters | Lymphocytes count | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Any Abnormality in Hematology Parameters | Monocytes count | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Any Abnormality in Hematology Parameters | Platelet count | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Any Abnormality in Hematology Parameters | Eosinophils count | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Any Abnormality in Hematology Parameters | MCV | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Any Abnormality in Hematology Parameters | Monocytes count | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Any Abnormality in Hematology Parameters | Basophils count | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Any Abnormality in Hematology Parameters | Hematocrit | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Any Abnormality in Hematology Parameters | Hemoglobin | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Any Abnormality in Hematology Parameters | Lymphocytes count | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Any Abnormality in Hematology Parameters | WBC count | 1 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Any Abnormality in Hematology Parameters | MCHC | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Any Abnormality in Hematology Parameters | Erythrocyte count | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Any Abnormality in Hematology Parameters | Neutrophils count | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Any Abnormality in Hematology Parameters | MCH | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Any Abnormality in Hematology Parameters | Platelet count | 0 Participants |
Secondary
Number of Participants With Any Abnormality in Vital Signs
Systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate, respiration rate and body temperature were measured in semi-supine position after 5 minutes rest. The clinically acceptable range included; SBP: 85 millimeters of mercury (mmHg) to 160 mmHg; DBP: 45 mmHg to 100 mmHg; pulse rate: 40 beats per minute to 110 beats per minute; respiration rate: 8 breaths per minute to 20 breaths per minute; body temperature: 35.5 degrees Celsius to 37.8 degrees Celsius. Number of participants with any abnormality in vital signs are presented.
Time frame: Up to Day 22
Population: Safety Analysis Set Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Griseofulvin 500 mg (T1) | Number of Participants With Any Abnormality in Vital Signs | Respiration rate | 0 Participants |
| Griseofulvin 500 mg (T1) | Number of Participants With Any Abnormality in Vital Signs | Pulse rate | 0 Participants |
| Griseofulvin 500 mg (T1) | Number of Participants With Any Abnormality in Vital Signs | SBP | 0 Participants |
| Griseofulvin 500 mg (T1) | Number of Participants With Any Abnormality in Vital Signs | DBP | 0 Participants |
| Griseofulvin 500 mg (T1) | Number of Participants With Any Abnormality in Vital Signs | Body temperature | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Any Abnormality in Vital Signs | Pulse rate | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Any Abnormality in Vital Signs | SBP | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Any Abnormality in Vital Signs | DBP | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Any Abnormality in Vital Signs | Respiration rate | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Any Abnormality in Vital Signs | Body temperature | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Any Abnormality in Vital Signs | Body temperature | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Any Abnormality in Vital Signs | Respiration rate | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Any Abnormality in Vital Signs | SBP | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Any Abnormality in Vital Signs | Pulse rate | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Any Abnormality in Vital Signs | DBP | 0 Participants |
Secondary
Number of Participants With Any Serious Adverse Event (SAE) and Any Non-serious Adverse Event (Non-SAE)
An adverse event was any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the medicinal product. An SAE was any untoward medical occurrence resulting in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, congenital anomaly/birth defect or any other other important medical event that may jeopardize the participant or may require medical or surgical treatment to prevent one of the other outcomes listed before.
Time frame: Up to Day 22
Population: Safety Analysis Set Population comprised of all randomized participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Griseofulvin 500 mg (T1) | Number of Participants With Any Serious Adverse Event (SAE) and Any Non-serious Adverse Event (Non-SAE) | Any SAE | 0 Participants |
| Griseofulvin 500 mg (T1) | Number of Participants With Any Serious Adverse Event (SAE) and Any Non-serious Adverse Event (Non-SAE) | Any non-SAE | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Any Serious Adverse Event (SAE) and Any Non-serious Adverse Event (Non-SAE) | Any SAE | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Any Serious Adverse Event (SAE) and Any Non-serious Adverse Event (Non-SAE) | Any non-SAE | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Any Serious Adverse Event (SAE) and Any Non-serious Adverse Event (Non-SAE) | Any SAE | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Any Serious Adverse Event (SAE) and Any Non-serious Adverse Event (Non-SAE) | Any non-SAE | 1 Participants |
Secondary
Number of Participants With Positive Results in Serum Beta-human Chorionic Gonadotropin (Beta-hCG) Level (Females Participants)
Blood samples were collected at indicated time points for assessment of serum beta-hCG (serum pregnancy test) for female participants. Number of participants with positive results in serum beta-hCG levels are presented.
Time frame: Days -1, 7, 17 and 22
Population: Safety Analysis Set Population. Only those participants with data available at the specified time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Griseofulvin 500 mg (T1) | Number of Participants With Positive Results in Serum Beta-human Chorionic Gonadotropin (Beta-hCG) Level (Females Participants) | Day -1 | 0 Participants |
| Griseofulvin 500 mg (T1) | Number of Participants With Positive Results in Serum Beta-human Chorionic Gonadotropin (Beta-hCG) Level (Females Participants) | Day 7 | 0 Participants |
| Griseofulvin 500 mg (T1) | Number of Participants With Positive Results in Serum Beta-human Chorionic Gonadotropin (Beta-hCG) Level (Females Participants) | Day 17 | 0 Participants |
| Griseofulvin 500 mg (T1) | Number of Participants With Positive Results in Serum Beta-human Chorionic Gonadotropin (Beta-hCG) Level (Females Participants) | Day 22 | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Positive Results in Serum Beta-human Chorionic Gonadotropin (Beta-hCG) Level (Females Participants) | Day 22 | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Positive Results in Serum Beta-human Chorionic Gonadotropin (Beta-hCG) Level (Females Participants) | Day -1 | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Positive Results in Serum Beta-human Chorionic Gonadotropin (Beta-hCG) Level (Females Participants) | Day 17 | 0 Participants |
| Griseofulvin 250 mg (T2) | Number of Participants With Positive Results in Serum Beta-human Chorionic Gonadotropin (Beta-hCG) Level (Females Participants) | Day 7 | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Positive Results in Serum Beta-human Chorionic Gonadotropin (Beta-hCG) Level (Females Participants) | Day 22 | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Positive Results in Serum Beta-human Chorionic Gonadotropin (Beta-hCG) Level (Females Participants) | Day 7 | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Positive Results in Serum Beta-human Chorionic Gonadotropin (Beta-hCG) Level (Females Participants) | Day 17 | 0 Participants |
| Griseofulvin 500 mg (R) | Number of Participants With Positive Results in Serum Beta-human Chorionic Gonadotropin (Beta-hCG) Level (Females Participants) | Day -1 | 0 Participants |