India Dexamethasone and Betamethasone

NCT03668860 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: CIN001 - India Steroids
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

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.

Conditions

Preterm Birth; Antenatal Corticosteroids

Keywords

Antenatal Corticosteroids; Betamethasone; Dexamethasone

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Adverse Events

  23 days

Study Arms (8)

Treatments A & B (6 subjects)

ACTIVE COMPARATOR

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; Drug: Betamethasone 4 mg/ml

Treatments B & A (6 subjects)

ACTIVE COMPARATOR

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; Drug: Betamethasone 4 mg/ml

Treatments C & D (6 subjects)

ACTIVE COMPARATOR

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; Drug: Dexamethasone Oral Tablet

Treatments D & C (6 subjects)

ACTIVE COMPARATOR

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; Drug: Dexamethasone Oral Tablet

Treatments E & D (6 subjects)

ACTIVE COMPARATOR

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; Drug: Betamethasone Oral Tablet

Treatments D & E (6 subjects)

ACTIVE COMPARATOR

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; Drug: Betamethasone Oral Tablet

Treatments C & E (6 subjects)

ACTIVE COMPARATOR

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; Drug: Betamethasone Oral Tablet

Treatments E & C (6 subjects)

ACTIVE COMPARATOR

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; Drug: Betamethasone Oral Tablet

Interventions

Dexamethasone 4 mg/ml DRUG

Intramuscular. Total dose: 1.5 mL (6 mg)

Treatments A & B (6 subjects); Treatments B & A (6 subjects)

Betamethasone 4 mg/ml DRUG

Intramuscular. Total dose: 1.5 mL (6 mg)

Treatments A & B (6 subjects); Treatments B & A (6 subjects)

Celestone Soluspan 6Mg/Ml Suspension for Injection DRUG

Intramuscular. Total dose: 1 mL (6 mg)

Treatments C & D (6 subjects); Treatments C & E (6 subjects); Treatments D & C (6 subjects); Treatments E & C (6 subjects)

Dexamethasone Oral Tablet DRUG

Oral. Total dose: 12 Tablets (6 mg)

Treatments C & D (6 subjects); Treatments D & C (6 subjects); Treatments D & E (6 subjects); Treatments E & D (6 subjects)

Betamethasone Oral Tablet DRUG

Oral. Total dose: 12 Tablets (6 mg)

Treatments C & E (6 subjects); Treatments D & E (6 subjects); Treatments E & C (6 subjects); Treatments E & D (6 subjects)

Eligibility Criteria

• Age: 18 Years - 40 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• \- 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).
• \- Subject should be literate.

You may not qualify if:

• \- 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.
• \- Major illness during 3 months before screening.
• \- Subjects who have participated in another clinical study in the past 3 months prior to commencement of this study.
• \- Any difficulty in accessibility of forearm veins for cannulation or blood sampling and or difficulty with donating blood.
• \- 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.
• \- Refuse to abstain from fluid for at least 1 h before and 1 h after dosing.

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• Bill and Melinda Gates Foundation: collaborator
• Syngene: collaborator

Study Sites (1)

Syngene International Limited, Tower I

Bangalore, 560 100, India

Location

MeSH Terms

Conditions

Premature Birth

Interventions

Dexamethasone; Betamethasone; betamethasone acetate phosphate; Suspensions; Injections

Condition Hierarchy (Ancestors)

Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Alan Jobe, MD, Ph.D

  Children's Hospital Medical Center, Cincinnati

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2018
• First Posted: September 13, 2018
• Study Start: September 20, 2018
• Primary Completion: February 28, 2019
• Study Completion: December 31, 2019
• Last Updated: July 14, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)