Drug-drug Interaction (DDI) Study of Spironolactone (Perpetrator) and Digoxin (Substrate Drug)

NCT03909529 | Completed Phase 1 Results FDA Drug

• 1 other identifier: C-CMP-SPI-001
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

An open label, balanced, randomized, single-dose, two-treatment, two-sequence, two-period, crossover oral drug-drug interaction study of spironolactone (perpetrator) and Digoxin (substrate drug) in healthy adult human subjects under fasting condition.

Conditions

Drug Drug Interaction

Outcome Measures

Primary Outcomes (2)

• Dogoxin Plasma Data for Cmax

  Primary Pharmacokinetic parameter The following pharmacokinetic parameters for Digoxin were obtained using non-compartmental method Cmax, AUC0-96, and tmax using plasma data, Renal clearance (CLR) /Percent Recovered, Unchanged drug excreted in urine (fe)/Amount Recovered using urine data.

  4 days

• Digoxin Plasma Data for AUC0-96

  Area under the plasma concentration versus time curve from time 0 to the 96 hour time point concentration.

  4 days

Secondary Outcomes (2)

• Digoxin Plasma Data for Tmax

  4 days

• ECG Measurement Will be Performed to Evaluate Any Changes in the QT Interval

  4 days

Other Outcomes (2)

• Renal Clearance (CLR)/Percent Recovered

  04 Days

• Unchanged Drug Excreted in Urine (fe)/ Amount Recovered

  04 Days

Study Arms (2)

LANOXIN® (Digoxin) USP 250 mcg (substrate drug) {Treatment A}

EXPERIMENTAL

14 Subjects first administered with LANOXIN® (digoxin) USP 250 mcg (Substrate drug) on Day 6 of in house, after overnight fasting of at least 10.00 hours. After washout period of 28 days, these 14 subjects were administered with Spironolactone Oral Suspension 100 mg (perpetrator, Carospir® Oral Suspension 20 mL of 25 mg / 5 mL) from day 1 to day 5 and on day 6 the after overnight fasting of at least 10.00 hours, subject was administered with LANOXIN® (digoxin) USP 250 mcg (substrate drug) + Spironolactone Oral Suspension 100 mg (perpetrator; Carospir® Oral Suspension 20 mL of 25 mg / 5 mL). From day 7 to day 9 the subjects were administered with Spironolactone Oral Suspension 100 mg (perpetrator; Carospir® Oral Suspension 20 mL of 25 mg / 5 mL).

Drug: Digoxin 250 MCG Oral Tablet

LANOXIN® (Digoxin) USP 250mcg and Carospir® Oral Suspension 20mL of 25 mg/5mL-Treatment B

EXPERIMENTAL

14 Subjects first administered with Spironolactone Oral Suspension 100 mg (perpetrator, Carospir® Oral Suspension 20 mL of 25 mg / 5 mL) from day 1 to day 5 and on day 6 the after overnight fasting of at least 10.00 hours, subject was administered with LANOXIN® (digoxin) USP 250 mcg (substrate drug) + Spironolactone Oral Suspension 100 mg (perpetrator; Carospir® Oral Suspension 20 mL of 25 mg / 5 mL). From day 7 to day 9 the subjects were administered with Spironolactone Oral Suspension 100 mg (perpetrator; Carospir® Oral Suspension 20 mL of 25 mg / 5 mL). After washout period of 28 days these 14 Subjects administered with LANOXIN® (digoxin) USP 250 mcg (Substrate drug) on Day 6 of in house, after overnight fasting of at least 10.00 hours

Drug: Spironolactone 25 mg/ 5 mL S/F Suspension

Interventions

Digoxin 250 MCG Oral Tablet DRUG

The intervention is for study of drug drug interaction of digoxin when administered with spironolactone oral suspension

Also known as: Spironolactone Oral Suspension 20 mL of 25 mg/mL

LANOXIN® (Digoxin) USP 250 mcg (substrate drug) {Treatment A}

Spironolactone 25 mg/ 5 mL S/F Suspension DRUG

The intervention is for study of drug drug interaction of digoxin when administered with spironolactone oral suspension

Also known as: DDI Spironolactone oral suspension interaction with digoxin

LANOXIN® (Digoxin) USP 250mcg and Carospir® Oral Suspension 20mL of 25 mg/5mL-Treatment B

Eligibility Criteria

• Age: 20 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy human subjects aged between 20 and 35 years (including both).
• Subjects with a BMI between 18.5 - 24.9 Kg/m2 (including both) but body weight not less than 60 Kgs.
• Subjects who were screened at least 48 hours prior to check-in
• Subjects with normal health as determined by personal medical history, clinical examination, and laboratory examinations including serological tests during the screening
• Subjects with normal 2D echo
• Subjects having normal 12-lead electrocardiogram (ECG) or ECG with no clinical significant abnormalities as determined by Investigator.
• Subjects having normal chest X-Ray (P/A view) or chest X-ray with no clinically significant abnormalities as determined by investigator.
• Subjects able to communicate effectively.
• Subjects willing to give written informed consent and adhere to all the requirements of this protocol.

You may not qualify if:

• Subjects having contraindications or hypersensitivity to study drug or related group of drugs.
• History or presence of any medical condition or disease according to the opinion of the physician.
• History or presence of significant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, endocrine, immunological, dermatological, neurological or psychiatric disease or disorder.
• Subject having QT/ corrected QT interval (QTc) \>450 milliseconds
• History or presence of significant alcoholism or drug abuse in the past one year.
• History or presence of significant smoking (more than 10 cigarettes /day or consumption of tobacco products).
• Subjects who fail to abstain from consuming any alcoholic products from 48.00 hours prior to check-in to till check-out / last sample of the study.
• Subjects who fail to abstain from any xanthine-containing food and/or beverages (like chocolate, tea, coffee, cola drinks), cigarettes and tobacco containing products and grapefruit and/or it's juice from 48.00 hours prior to check-in to till check-out / last sample of the study.
• Subjects who fail to refrain from pan or pan masala, gutkha, masala (containing beetle nut and tobacco) for 48.00 hours prior to check-in to till check-out/last sample of the study.
• Difficulty with donating blood.
• Systolic blood pressure less than 110 mm Hg or more than 140 mm Hg.
• Diastolic blood pressure less than 70 mm Hg or more than 90 mm Hg.
• Pulse rate less than 60 beats/minute or more than 100 beats/minute.
• Use of any prescribed medication during last two weeks or over-the- counter (OTC) medicinal products/ herbal products during the last one week prior to check-in.
• Major illness during 90 days before check-in.

Sponsors & Collaborators

• CMP Development, LLC: lead

Study Sites (1)

ClinSync Clinical Research Pvt. Ltd.

Hyderabad, Telangana, 501505, India

Location

MeSH Terms

Interventions

Digoxin; Tablets; Spironolactone

Intervention Hierarchy (Ancestors)

Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates; Dosage Forms; Pharmaceutical Preparations; Lactones; Organic Chemicals; Pregnenes; Pregnanes

Results Point of Contact

• Title: Paul Sudhakar
• Organization: CMP Pharma

pauls@ptspharma.com

816-507-8249

Study Officials

• Roopali K Somani, MD

  Employee

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Spironolactone Oral Suspension
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: An open label, balanced, randomized, single-dose, two-treatment, two-sequence, two-period, crossover, drug-drug interaction study in healthy adult human subjects under fasting condition for spironolactone oral suspension (Carospir®)

Study Record Dates

• First Submitted: February 16, 2019
• First Posted: April 10, 2019
• Study Start: March 10, 2019
• Primary Completion: April 19, 2019
• Study Completion: April 30, 2019
• Last Updated: May 1, 2023
• Results First Posted: May 1, 2023

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)