A Phase 1, Open-Label, Randomized Study to Compare the Pharmacokinetics and Pharmacodynamics of Single Dose Dexamethasone and Betamethasone Administered Orally and Intramuscularly in Healthy Female Subjects
Overview
- Phase
- Phase 1
- Intervention
- Dexamethasone 4 mg/ml
- Conditions
- Preterm Birth
- Sponsor
- Children's Hospital Medical Center, Cincinnati
- Enrollment
- 48
- Locations
- 1
- Primary Endpoint
- Measurements of pharmacokinetic parameters of each drug
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
An open label, randomized, two-period, crossover, study to compare the pharmacokinetics and pharmacodynamics of single dose Dexamethasone and Betamethasone administered orally and intramuscularly in 48 healthy, adult, female subjects under fasting conditions. This study is being conducted in Bangalore, India.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy, adult, female subjects within the age range of 18 to 40 years \[both inclusive\].
- •Weight not less than 45 kg.
- •BMI \[18.00 to 25.00 kg/m2\] \[both inclusive\].
- •Willingness to provide written informed consent to participate in the study.
- •Without any medical or surgical condition that might interfere with gastrointestinal absorption of the study drug.
- •Free of significant diseases or clinically significant abnormal findings during screening, medical history, physical examination, laboratory evaluations, 12-lead ECG, Chest X-ray \[PA view\].
- •Subjects should be non-smoker or moderate smokers (less than 10 cigarettes a day), and should not be consuming tobacco containing products \[ defined as someone who has stopped smoking for a year from the date of screening\].
- •Subject must be either a non-drinker or an occasional drinker of alcohol and agreed to abstain from alcoholic consumption during the study duration.
- •Absence of disease markers of HIV I and 2, Hepatitis Band C and Syphilis.
- •Female subjects of childbearing potential must be using two acceptable methods of contraception, ( e.g., intra-uterine device (IUD) plus condom, spermicidal gel plus condom, diaphragm plus condom, progestin only implants and long acting injectables (Depo Provera), etc.). These measures are required during the study and for at least two weeks after the last dose and conveyed during the inform consent process (or) postmenopausal women for at least 1 year or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy have been performed).
Exclusion Criteria
- •History or presence of significant: Cardiovascular, pulmonary, hepatic, renal, hematological, gastro- intestinal, endocrine, immunologic, dermatologic, neurological, HEENT (Head, Eyes, Ears, Nose And Throat), psychiatric disease/ disorder.
- •History or presence of significant:
- •Asthma, urticaria or other allergic type reactions or hypersensitivity after taking Dexamethasone or Betamethasone or any other drug.
- •Ulceration or history of gastric and / or duodenal ulcer.
- •Stomach or intestinal bleeding.
- •Jaundice in the past 6 months.
- •History of drug abuse.
- •History of renal impairment or severe hepatic impairment.
- •History or presence of psychiatric disorders
- •Have donated 500 mL or more blood within 90 days before receiving the first dose of study drug.
Arms & Interventions
Treatments A & B (6 subjects)
After overnight fasting of at least 10 hours, a single dose of investigational product A will be administered intramuscularly at gluteal or thigh region to each subject in this arm. Following washout period of between 9-12 days and after overnight fasting of at least 10 hours, a single dose of investigational product B will be administered intramuscularly at gluteal or thigh region to each subject in this arm. (Treatment A: Dexamethasone sodium phosphate intramuscular injection, 4mg/mL - Total dose: 1.5mL (6mg)) (Treatment B: Betamethasone phosphate solution intramuscular injection, 4mg/mL - Total dose: 1.5mL (6mg))
Intervention: Dexamethasone 4 mg/ml
Treatments A & B (6 subjects)
After overnight fasting of at least 10 hours, a single dose of investigational product A will be administered intramuscularly at gluteal or thigh region to each subject in this arm. Following washout period of between 9-12 days and after overnight fasting of at least 10 hours, a single dose of investigational product B will be administered intramuscularly at gluteal or thigh region to each subject in this arm. (Treatment A: Dexamethasone sodium phosphate intramuscular injection, 4mg/mL - Total dose: 1.5mL (6mg)) (Treatment B: Betamethasone phosphate solution intramuscular injection, 4mg/mL - Total dose: 1.5mL (6mg))
Intervention: Betamethasone 4 mg/ml
Treatments B & A (6 subjects)
After overnight fasting of at least 10 hours, a single dose of investigational product B will be administered intramuscularly at gluteal or thigh region to each subject in this arm. Following washout period of between 9-12 days and after overnight fasting of at least 10 hours, a single dose of investigational product A will be administered intramuscularly at gluteal or thigh region to each subject in this arm. (Treatment B: Betamethasone phosphate solution intramuscular injection, 4mg/mL - Total dose: 1.5mL (6mg)) (Treatment A: Dexamethasone sodium phosphate intramuscular injection, 4mg/mL - Total dose: 1.5mL (6mg))
Intervention: Dexamethasone 4 mg/ml
Treatments B & A (6 subjects)
After overnight fasting of at least 10 hours, a single dose of investigational product B will be administered intramuscularly at gluteal or thigh region to each subject in this arm. Following washout period of between 9-12 days and after overnight fasting of at least 10 hours, a single dose of investigational product A will be administered intramuscularly at gluteal or thigh region to each subject in this arm. (Treatment B: Betamethasone phosphate solution intramuscular injection, 4mg/mL - Total dose: 1.5mL (6mg)) (Treatment A: Dexamethasone sodium phosphate intramuscular injection, 4mg/mL - Total dose: 1.5mL (6mg))
Intervention: Betamethasone 4 mg/ml
Treatments C & D (6 subjects)
After overnight fasting of at least 10 hours, a single dose of investigational product C will be administered intramuscularly at gluteal or thigh region to each subject in this arm. Following washout period of between 9-12 days and after overnight fasting of at least 10 hours, a single dose of investigational product D will be administered orally with 240± 2mL of water in sitting posture at room temperature to each subject in this arm. (Treatment C: Celestone Soluspan intramuscular injection, 6mg/mL (3mg phosphate and 3 mg acetate salts) - Total dose: 1mL (6mg)) (Treatment D: Dexamethasone phosphate 0.5mg oral tablets - Total dose: 12 tablets (6mg))
Intervention: Celestone Soluspan 6Mg/Ml Suspension for Injection
Treatments C & D (6 subjects)
After overnight fasting of at least 10 hours, a single dose of investigational product C will be administered intramuscularly at gluteal or thigh region to each subject in this arm. Following washout period of between 9-12 days and after overnight fasting of at least 10 hours, a single dose of investigational product D will be administered orally with 240± 2mL of water in sitting posture at room temperature to each subject in this arm. (Treatment C: Celestone Soluspan intramuscular injection, 6mg/mL (3mg phosphate and 3 mg acetate salts) - Total dose: 1mL (6mg)) (Treatment D: Dexamethasone phosphate 0.5mg oral tablets - Total dose: 12 tablets (6mg))
Intervention: Dexamethasone Oral Tablet
Treatments D & C (6 subjects)
After overnight fasting of at least 10 hours, a single dose of investigational product D will be administered orally with 240± 2mL of water in sitting posture at room temperature to each subject in this arm. Following washout period of between 9-12 days and after overnight fasting of at least 10 hours, a single dose of investigational product C will be administered intramuscularly at gluteal or thigh region to each subject in this arm. (Treatment D: Dexamethasone phosphate 0.5mg oral tablets - Total dose: 12 tablets (6mg)) (Treatment C: Celestone Soluspan intramuscular injection, 6mg/mL (3mg phosphate and 3 mg acetate salts) - Total dose 1mL (6mg))
Intervention: Celestone Soluspan 6Mg/Ml Suspension for Injection
Treatments D & C (6 subjects)
After overnight fasting of at least 10 hours, a single dose of investigational product D will be administered orally with 240± 2mL of water in sitting posture at room temperature to each subject in this arm. Following washout period of between 9-12 days and after overnight fasting of at least 10 hours, a single dose of investigational product C will be administered intramuscularly at gluteal or thigh region to each subject in this arm. (Treatment D: Dexamethasone phosphate 0.5mg oral tablets - Total dose: 12 tablets (6mg)) (Treatment C: Celestone Soluspan intramuscular injection, 6mg/mL (3mg phosphate and 3 mg acetate salts) - Total dose 1mL (6mg))
Intervention: Dexamethasone Oral Tablet
Treatments E & D (6 subjects)
After overnight fasting of at least 10 hours, a single dose of investigational product E will be administered orally with 240± 2mL of water in sitting posture at room temperature to each subject in this arm. Following washout period of between 9-12 days and after overnight fasting of at least 10 hours, a single dose of investigational product D will be administered orally with 240± 2mL of water in sitting posture at room temperature to each subject in this arm. (Treatment E: Betamethasone phosphate 0.5mg oral tablets - Total dose: 12 tablets (6mg)) (Treatment D: Dexamethasone phosphate 0.5mg oral tablets - Total dose: 12 tablets (6mg))
Intervention: Dexamethasone Oral Tablet
Treatments E & D (6 subjects)
After overnight fasting of at least 10 hours, a single dose of investigational product E will be administered orally with 240± 2mL of water in sitting posture at room temperature to each subject in this arm. Following washout period of between 9-12 days and after overnight fasting of at least 10 hours, a single dose of investigational product D will be administered orally with 240± 2mL of water in sitting posture at room temperature to each subject in this arm. (Treatment E: Betamethasone phosphate 0.5mg oral tablets - Total dose: 12 tablets (6mg)) (Treatment D: Dexamethasone phosphate 0.5mg oral tablets - Total dose: 12 tablets (6mg))
Intervention: Betamethasone Oral Tablet
Treatments D & E (6 subjects)
After overnight fasting of at least 10 hours, a single dose of investigational product D will be administered orally with 240± 2mL of water in sitting posture at room temperature to each subject in this arm. Following washout period of between 9-12 days and after overnight fasting of at least 10 hours, a single dose of investigational product E will be administered orally with 240± 2mL of water in sitting posture at room temperature to each subject in this arm. (Treatment D: Dexamethasone phosphate 0.5mg oral tablets - Total dose: 12 tablets (6mg)) (Treatment E: Betamethasone phosphate 0.5mg oral tablets - Total dose: 12 tablets (6mg))
Intervention: Dexamethasone Oral Tablet
Treatments D & E (6 subjects)
After overnight fasting of at least 10 hours, a single dose of investigational product D will be administered orally with 240± 2mL of water in sitting posture at room temperature to each subject in this arm. Following washout period of between 9-12 days and after overnight fasting of at least 10 hours, a single dose of investigational product E will be administered orally with 240± 2mL of water in sitting posture at room temperature to each subject in this arm. (Treatment D: Dexamethasone phosphate 0.5mg oral tablets - Total dose: 12 tablets (6mg)) (Treatment E: Betamethasone phosphate 0.5mg oral tablets - Total dose: 12 tablets (6mg))
Intervention: Betamethasone Oral Tablet
Treatments C & E (6 subjects)
After overnight fasting of at least 10 hours, a single dose of investigational product C will be administered intramuscularly at gluteal or thigh region to each subject in this arm. Following washout period of between 9-12 days and after overnight fasting of at least 10 hours, a single dose of investigational product E will be administered orally with 240± 2mL of water in sitting posture at room temperature to each subject in this arm. C: Celestone Soluspan intramuscular injection, 6mg/mL (3mg phosphate and 3 mg acetate salts) - Total dose 1mL (6mg) E: Betamethasone phosphate 0.5mg oral tablets - Total dose: 12 tablets (6mg)
Intervention: Celestone Soluspan 6Mg/Ml Suspension for Injection
Treatments C & E (6 subjects)
After overnight fasting of at least 10 hours, a single dose of investigational product C will be administered intramuscularly at gluteal or thigh region to each subject in this arm. Following washout period of between 9-12 days and after overnight fasting of at least 10 hours, a single dose of investigational product E will be administered orally with 240± 2mL of water in sitting posture at room temperature to each subject in this arm. C: Celestone Soluspan intramuscular injection, 6mg/mL (3mg phosphate and 3 mg acetate salts) - Total dose 1mL (6mg) E: Betamethasone phosphate 0.5mg oral tablets - Total dose: 12 tablets (6mg)
Intervention: Betamethasone Oral Tablet
Treatments E & C (6 subjects)
After overnight fasting of at least 10 hours, a single dose of investigational product E will be administered orally with 240± 2mL of water in sitting posture at room temperature to each subject in this arm. Following washout period of between 9-12 days and after overnight fasting of at least 10 hours, a single dose of investigational product C will be administered intramuscularly at gluteal or thigh region to each subject in this arm. E: Betamethasone phosphate 0.5mg oral tablets - Total dose: 12 tablets (6mg) C: Celestone Soluspan intramuscular injection, 6mg/mL (3mg phosphate and 3 mg acetate salts) - Total dose 1mL (6mg)
Intervention: Celestone Soluspan 6Mg/Ml Suspension for Injection
Treatments E & C (6 subjects)
After overnight fasting of at least 10 hours, a single dose of investigational product E will be administered orally with 240± 2mL of water in sitting posture at room temperature to each subject in this arm. Following washout period of between 9-12 days and after overnight fasting of at least 10 hours, a single dose of investigational product C will be administered intramuscularly at gluteal or thigh region to each subject in this arm. E: Betamethasone phosphate 0.5mg oral tablets - Total dose: 12 tablets (6mg) C: Celestone Soluspan intramuscular injection, 6mg/mL (3mg phosphate and 3 mg acetate salts) - Total dose 1mL (6mg)
Intervention: Betamethasone Oral Tablet
Outcomes
Primary Outcomes
Measurements of pharmacokinetic parameters of each drug
Time Frame: 23 days
Plasma concentration versus time curves of Dexamethasone and Betamethasone given orally and intramuscularly to non-pregnant females.
Measurements of pharmacodynamic parameters of each drug
Time Frame: 23 days
Measurements of glucose, cortisol and lymphocyte population changes versus time resulting from the steroid treatment given orally and intramuscularly to non-pregnant females.
Secondary Outcomes
- Adverse Events(23 days)