India Dexamethasone and Betamethasone

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

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.

Study Overview

• Status: Completed
• Conditions: Preterm Birth; Antenatal Corticosteroids
• Intervention / Treatment: Drug: Dexamethasone 4 mg/ml; Drug: Betamethasone 4 mg/ml; Drug: Celestone Soluspan 6Mg/Ml Suspension for Injection; Drug: Dexamethasone Oral Tablet; Drug: Betamethasone Oral Tablet

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• India
  • Bangalore, India, 560 100
    • Syngene International Limited, Tower I

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 38 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. - Healthy, adult, female subjects within the age range of 18 to 40 years [both inclusive].
2. - Weight not less than 45 kg.
3. - BMI [18.00 to 25.00 kg/m2] [both inclusive].
4. - Willingness to provide written informed consent to participate in the study.
5. - Without any medical or surgical condition that might interfere with gastrointestinal absorption of the study drug.
6. - 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].
7. - 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].
8. - Subject must be either a non-drinker or an occasional drinker of alcohol and agreed to abstain from alcoholic consumption during the study duration.
9. - Absence of disease markers of HIV I and 2, Hepatitis Band C and Syphilis.
10. - 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).
11. - Subject should be literate.

Exclusion Criteria:

1. - 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.

2. - 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.
3. - History of drug abuse.
4. - History of renal impairment or severe hepatic impairment.
5. - History or presence of psychiatric disorders
6. - Have donated 500 mL or more blood within 90 days before receiving the first dose of study drug.
7. - Major illness during 3 months before screening.
8. - Subjects who have participated in another clinical study in the past 3 months prior to commencement of this study.
9. - Any difficulty in accessibility of forearm veins for cannulation or blood sampling and or difficulty with donating blood.
10. - Refuse to abstain from food for at least 10 h prior to dosing and for at least 4 h after dosing in each period and for at least 10 h before and at least 4 h after collecting the baseline assessment blood sample in Period 1.
11. - Refuse to abstain from fluid for at least 1 h before and 1 h after dosing.
12. - Refuse to abstain from alcohol for the duration of the study.
13. - Positive during breath alcohol test.
14. - Positive during urine drug screening.
15. - History of difficulty in swallowing study formulations.
16. - Received any medication [including over-the-counter products, vitamins, herbal products] for 14 days preceding the study.
17. - Use of enzyme modifying drugs, MAO inhibitors within 30 days prior to receiving the first dose of study medication.
18. - History of dehydration from diarrhea, vomiting or any other reason within a period of 24 hours prior to study check-in of each period.
19. - Consumption of xanthine containing food and beverages (chocolates, tea, coffee or cola drinks) for at least 48 hours prior to study check-in.
20. - Consumption of grapefruit juice within the 7-days prior to study check-in.
21. - Pregnant females as determined by positive test for pregnancy.
22. - Lactating females.
23. - Investigator/physician feels that it is not in the subject's and/or study's best interest to enroll the subject.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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))	Drug: Dexamethasone 4 mg/ml; Intramuscular. Total dose: 1.5 mL (6 mg); Drug: Betamethasone 4 mg/ml; Intramuscular. Total dose: 1.5 mL (6 mg)
Active Comparator: 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))	Drug: Dexamethasone 4 mg/ml; Intramuscular. Total dose: 1.5 mL (6 mg); Drug: Betamethasone 4 mg/ml; Intramuscular. Total dose: 1.5 mL (6 mg)
Active Comparator: 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))	Drug: Celestone Soluspan 6Mg/Ml Suspension for Injection; Intramuscular. Total dose: 1 mL (6 mg); Drug: Dexamethasone Oral Tablet; Oral. Total dose: 12 Tablets (6 mg)
Active Comparator: 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))	Drug: Celestone Soluspan 6Mg/Ml Suspension for Injection; Intramuscular. Total dose: 1 mL (6 mg); Drug: Dexamethasone Oral Tablet; Oral. Total dose: 12 Tablets (6 mg)
Active Comparator: 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))	Drug: Dexamethasone Oral Tablet; Oral. Total dose: 12 Tablets (6 mg); Drug: Betamethasone Oral Tablet; Oral. Total dose: 12 Tablets (6 mg)
Active Comparator: 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))	Drug: Dexamethasone Oral Tablet; Oral. Total dose: 12 Tablets (6 mg); Drug: Betamethasone Oral Tablet; Oral. Total dose: 12 Tablets (6 mg)
Active Comparator: 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)	Drug: Celestone Soluspan 6Mg/Ml Suspension for Injection; Intramuscular. Total dose: 1 mL (6 mg); Drug: Betamethasone Oral Tablet; Oral. Total dose: 12 Tablets (6 mg)
Active Comparator: 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)	Drug: Celestone Soluspan 6Mg/Ml Suspension for Injection; Intramuscular. Total dose: 1 mL (6 mg); Drug: Betamethasone Oral Tablet; Oral. Total dose: 12 Tablets (6 mg)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measurements of pharmacokinetic parameters of each drug	Plasma concentration versus time curves of Dexamethasone and Betamethasone given orally and intramuscularly to non-pregnant females.	23 days
Measurements of pharmacodynamic parameters of each drug	Measurements of glucose, cortisol and lymphocyte population changes versus time resulting from the steroid treatment given orally and intramuscularly to non-pregnant females.	23 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	To monitor the adverse events and to ensure the safety of the subjects. Safety assessments will be analyzed descriptively. All continuous variables will be summarized using the following descriptive statistics: n, mean, standard deviation, median, minimum value, and maximum value. Categorical variables will be summarized using frequency counts and percentages. No formal statistical inferences are planned.	23 days

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Collaborators: Bill and Melinda Gates Foundation; Syngene International
• Investigators: Study Director: Alan Jobe, MD, Ph.D, Children's Hospital Medical Center, Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2018
• Primary Completion (Actual): February 28, 2019
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: August 10, 2018
• First Submitted That Met QC Criteria: September 11, 2018
• First Posted (Actual): September 13, 2018

Study Record Updates

• Last Update Posted (Actual): July 14, 2020
• Last Update Submitted That Met QC Criteria: July 13, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Dexamethasone; Betamethasone; Antenatal Corticosteroids
• Additional Relevant MeSH Terms: Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Premature Birth; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Dexamethasone; Dexamethasone acetate; BB 1101; Betamethasone; Betamethasone Valerate; Betamethasone-17,21-dipropionate; Betamethasone benzoate; Betamethasone sodium phosphate; Betamethasone acetate phosphate
• Other Study ID Numbers: CIN001 - India Steroids

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes