Drug Drug InteractionPhase 1NCT03909529
Drug-drug Interaction (DDI) Study of Spironolactone (Perpetrator) and Digoxin (Substrate Drug)
A Phase 1 study testing Digoxin 250 MCG Oral Tablet and Spironolactone 25 mg/ 5 mL S/F Suspension in people with Drug Drug Interaction, run by CMP Development, LLC at 1 site in India.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Drug Drug Interaction
- What is being tested?
- Digoxin 250 MCG Oral Tablet and Spironolactone 25 mg/ 5 mL S/F Suspension
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteIndia
- Study dates
- 10 Mar 2019to 30 Apr 2019
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
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- 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.
- Additional inclusion criteria for female subjects, Female of childbearing potential practicing an acceptable method of birth control for the duration of the study as judged by the investigator(s), such as condoms, foams, jellies, diaphragm, intrauterine device (IUD), or abstinence: or Postmenopausal for at least 1 year, or Surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy has been performed on the subject).
Who cannot join
- 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).
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- 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.
- Participation in a drug research study within past 90 days of check-in.
- Donation of blood (i.e. one unit or 350 mL) in the past 90 days before check-in.
- History of unusual diet consumption in the past 3 weeks before check-in.
- Additional exclusion criteria for female subjects, Volunteer demonstrating a positive pregnancy test. Volunteers who are pregnant, currently breast-feeding or who are likely to become pregnant during the study.
- Volunteers who have used implanted or injected hormonal contraceptives anytime during the 6 months prior to study or used hormonal contraceptives within 14 days before dosing.
- -
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Two Way Crossover Oral Drug-drug Interaction Study of Spironolactone (Perpetrator) and Digoxin (Substrate Drug) in Healthy Adult Human Subjects Under Fasting Condition
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.
Read the detailed description
Drug interaction studies between spironolactone and digoxin, particularly studies in which digoxin was administered intravenously (Waldorf, S 1978; Fenster, P.E. 1984), indicate that spironolactone may decrease the renal clearance of digoxin by 18-25%, and increase the (area under curve) AUC of digoxin by 35-44%. Although the radioimmunoassay used in the study may be confounded, these results suggest that inhibition of P-gp in the renal proximal tubules may be possible. To account for possible renal P-gp inhibition, subjects in the test group will be pretreated with spironolactone for about 5 days to allow accumulation of some of the metabolites which have a long half-life (e.g., canrenone ~33 hours) and continue to be treated with spironolactone while digoxin is renally eliminated from the body. Based on this assessment, the FDA suggested study design is Treatment A: Single dose of digoxin alone. Treatment B: Digoxin + Spironolactone; Day 1- 9: Spironolactone single dose; Day 6: Digoxin single oral dose.
Also, digoxin has a long half-life of 1.5-2 days, and the Pharmacokinetic (PK) sampling scheme of up to 72 hours may not be enough to characterize the elimination kinetics of digoxin. Hence, the plasma concentrations of digoxin up to 96 hours (4 days) postdose is considered This will allow you to detect possible differences in the clearance of digoxin mediated by an interaction with P-gp in the renal proximal tubules.
The study also involves collecting urine samples and measuring renal clearance (CLR) and unchanged drug excreted in urine (fe) for digoxin.
- Conditions
- Drug Drug Interaction
- Being tested
- Digoxin 250 MCG Oral Tablet, Spironolactone 25 mg/ 5 mL S/F Suspension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Digoxin 250 MCG Oral TabletDrug
Also called Spironolactone Oral Suspension 20 mL of 25 mg/mL
The intervention is for study of drug drug interaction of digoxin when administered with spironolactone oral suspension
Spironolactone 25 mg/ 5 mL S/F SuspensionDrug
Also called DDI Spironolactone oral suspension interaction with digoxin
The intervention is for study of drug drug interaction of digoxin when administered with spironolactone oral suspension
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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 Receives: Drug: Spironolactone 25 mg/ 5 mL S/F Suspension |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 4 days
Secondary outcomes (2)
Digoxin Plasma Data for Tmax
If the maximum value occurs at more than one time point, Tmax is defined as the first time point with this value.
Measured: 4 days
ECG Measurement Will be Performed to Evaluate Any Changes in the QT Interval
ECG will be performed at 1.00 and 3.00 hours post dose in each period on Day 6 and at check-out of each period of the study
Measured: 4 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2019
- Study start10 Mar 2019
- Primary completion19 Apr 2019
- Study completion30 Apr 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Drug Drug InteractionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- 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®)
- Masking
- None (open label)
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- CMP Development, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Roopali K Somani, MD, Principal investigator, Employee
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03909529
- Sponsor's protocol ID
- C-CMP-SPI-001
- Status last verified
- Jun 2022
- First submitted
- 16 Feb 2019
- Last updated
- 1 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Two Way Crossover Oral Drug-drug Interaction Study of Spironolactone (Perpetrator) and Digoxin (Substrate Drug) in Healthy Adult Human Subjects Under Fasting Condition
- ClinicalTrials.gov ID
- NCT03909529
- Acronym / sponsor ID
- C-CMP-SPI-001
- Conditions
- Drug Drug Interaction
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- CMP Development, LLCIndustry (pharma, biotech, devices)
- Study start
- 10 Mar 2019 (actual)
- Primary completion
- 19 Apr 2019 (actual)
- Study completion
- 30 Apr 2019 (actual)
- First posted
- 10 Apr 2019 (actual)
- Results
- Posted 1 May 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Drug interaction studies between spironolactone and digoxin, particularly studies in which digoxin was administered intravenously (Waldorf, S 1978; Fenster, P.E. 1984), indicate that spironolactone may decrease the renal clearance of digoxin by 18-25%, and increase the (area under curve) AUC of digoxin by 35-44%. Although the radioimmunoassay used in the study may be confounded, these results suggest that inhibition of P-gp in the renal proximal tubules may be possible. To account for possible renal P-gp inhibition, subjects in the test group will be pretreated with spironolactone for about 5 days to allow accumulation of some of the metabolites which have a long half-life (e.g., canrenone ~33 hours) and continue to be treated with spironolactone while digoxin is renally eliminated from the body. Based on this assessment, the FDA suggested study design is Treatment A: Single dose of digoxin alone. Treatment B: Digoxin + Spironolactone; Day 1- 9: Spironolactone single dose; Day 6: Digoxin single oral dose.
Also, digoxin has a long half-life of 1.5-2 days, and the Pharmacokinetic (PK) sampling scheme of up to 72 hours may not be enough to characterize the elimination kinetics of digoxin. Hence, the plasma concentrations of digoxin up to 96 hours (4 days) postdose is considered This will allow you to detect possible differences in the clearance of digoxin mediated by an interaction with P-gp in the renal proximal tubules.
The study also involves collecting urine samples and measuring renal clearance (CLR) and unchanged drug excreted in urine (fe) for digoxin.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- 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®)
| Arm | Type | Receives |
|---|---|---|
| LANOXIN® (Digoxin) USP 250 mcg (substrate drug) {Treatment A} | Experimental | Drug: Digoxin 250 MCG Oral Tablet14 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). |
| LANOXIN® (Digoxin) USP 250mcg and Carospir® Oral Suspension 20mL of 25 mg/5mL-Treatment B | Experimental | Drug: Spironolactone 25 mg/ 5 mL S/F Suspension14 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 |
Who may qualify
- Ages
- 20 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (21 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Digoxin 250 MCG Oral TabletAlso: Spironolactone Oral Suspension 20 mL of 25 mg/mLThe intervention is for study of drug drug interaction of digoxin when administered with spironolactone oral suspension | Drug | LANOXIN® (Digoxin) USP 250 mcg (substrate drug) {Treatment A} |
| Spironolactone 25 mg/ 5 mL S/F SuspensionAlso: DDI Spironolactone oral suspension interaction with digoxinThe intervention is for study of drug drug interaction of digoxin when administered with spironolactone oral suspension | Drug | LANOXIN® (Digoxin) USP 250mcg and Carospir® Oral Suspension 20mL of 25 mg/5mL-Treatment B |
Primary outcome
Dogoxin Plasma Data for Cmax
Time frame: 4 days
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.
Digoxin Plasma Data for AUC0-96
Time frame: 4 days
Area under the plasma concentration versus time curve from time 0 to the 96 hour time point concentration.
2 secondary outcomes
Digoxin Plasma Data for Tmax
Time frame: 4 days
ECG Measurement Will be Performed to Evaluate Any Changes in the QT Interval
Time frame: 4 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roopali K Somani, MD principal investigator
Employee
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Digoxin 250 MCG Oral Tablet and Spironolactone 25 mg/ 5 mL S/F Suspension in people with Drug Drug Interaction, run by CMP Development, LLC at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dogoxin Plasma Data for Cmax (time frame: 4 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2023.