Evaluation of Drug Interactions of Saxagliptin With Sildenafil in Healthy Volunteers

NCT04170790 | Unknown

• 1 other identifier: 57
• Study Type: interventional
• Target: 18
• Locations: 0 countries
• Sites: N/A

Brief Summary

Patients with diabetes are three times more likely to develop erectile dysfunction (ED), and longer duration of diabetes is strongly associated with ED. The possibility of pharmacokinetic interactions may occur as the two drugs are metabolized by hepatic CYP3A4 and their co administration may affect their plasma concentrations. the aim of work is to investigate the effect of sildenafil a CYP3A4 substrate and inhibitor on the pharmacokinetics and safety of Saxagliptin, a CYP3A4 substrate Subjects and Methods: Eighteen healthy volunteers will be recruited in Sequential, single center study to determine pharmacokinetic parameters of Saxagliptin, and sildenafil,(AUC0→∞), (AUC0→t); Cmax; tmax; t½, k; ka) will be measured using validated LC-MS/MS method. Therapeutic doses will be given to volunteers as follows: Sildenafil 50 mg single dose on day 1, then washout period from day 2 till day 8. Saxagliptin 5 mg once/day will be given from day 9 till day 12, then on day 13 the two drugs will be co-administered. Blood samples (5ml) for pharmacokinetic analysis will be collected on days 1 and 13 for Sildenafil as well as on days 12 and 13 for Saxagliptin.

Conditions

Diabetes Mellitus, Type 2; Erectile Dysfunction With Diabetes Mellitus; Drug Interaction

Outcome Measures

Primary Outcomes (9)

• Cmax

  Maximum Plasma Concentration

  pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, and 24 hours post-dose.

• (AUC0→∞)

  Area Under Curve Infinity

  pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, and 24 hours post-dose.

• (AUC0→t)

  Area Under the Curve

  pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, and 24 hours post-dose.

• tmax;

  Time to reach Maximum concentration

  pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, and 24 hours post-dose.

• T½

  Drug half Life

  pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, and 24 hours post-dose.

• Ke

  Elimination Rate

  pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, and 24 hours post-dose.

• ka

  Absorption Rate

  pre-dose and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, and 24 hours post-dose.

• Blood Pressure

  changes in Systolic and Diastolic Blood Pressure from normal range

  measured before dosing and at 2, 4, 6, 8, and 10 hours after drug administration on each day of blood sampling

• Heart Rate

  Changes in heart rate from normal range

  measured before dosing and at 2, 4, 6, 8, and 10 hours after drug administration on each day of blood sampling

Study Arms (1)

Healthy volunteer

EXPERIMENTAL

Day 1: Sildenafil 50 mg single dose Day 2-Day 8: Washout period Day 9-12: Saxagliptin 5 mg Once/day Day 13: Sildenafil 50 mg+ Saxagliptin 5 mg

Drug: Saxagliptin 5mg; Drug: Sildenafil 50 mg

Interventions

Saxagliptin 5mg DRUG

Saxagliptin 5mg oral tablet

Also known as: Onglyza

Healthy volunteer

Sildenafil 50 mg DRUG

Sildenafil 50 mg Oral Tablet

Also known as: Viagra

Healthy volunteer

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-45 years.
• Ideal weight within the normal range according to accepted life tables.
• Non-contributory history and normal physiological examination.
• Laboratory data within normal limits.
• Performance and compliance.
• The subjects should be without known history of alcohol or drug abuse problems and should preferably be non-smokers.
• The volunteers will be asked to provide a complete medical history, and complete a physical examination, laboratory tests (hematology, clinical chemistry, urinalysis serology (including hepatitis B surface antigen, anti-hepatitis C virus and antihuman immunodeficiency virus antibody).

You may not qualify if:

• A known hypersensitivity to the drug.
• Gastrointestinal diseases.
• Auto immune diseases.
• Renal diseases or dysfunction.
• Cardiovascular disease of any type.
• Pancreatic disease including diabetes.
• Hepatic disease.
• Hematological, osteopathic, or pulmonary disease.
• History of alcoholism or drug abuse.
• Serious Psychological illness.
• Positive HIV-I.
• Smoking (if including they should be identified).
• Abnormal (out of range) laboratory values.
• Subject who have taken any medication (Rx or OTC) less than two weeks of the trials starting date.
• Subject who have donated blood or who have been in multiple dosing studies requiring a large volume of blood (more than 500 ml) to be drawn within six weeks preceding the start of the trials.

Sponsors & Collaborators

• Ain Shams University: lead

Related Publications (1)

• Mansour RY, ElBorolossy R, Shaheen SM, Sabri NA. Evaluation of drug interactions of saxagliptin with sildenafil in healthy volunteers. Eur J Clin Pharmacol. 2022 Dec;78(12):1935-1944. doi: 10.1007/s00228-022-03397-w. Epub 2022 Oct 10.

  PMID: 36214883 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

saxagliptin; Sildenafil Citrate

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Central Study Contacts

Rania Y Mansour, MD

CONTACT

0201000350066; rania.mansour@mehy-eg.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Masters Of Clinical Pharmacy- faculty of Pharmacy- Ain shams University

Model Details: Eighteen healthy volunteers will be recruited in Sequential, single center study to determine pharmacokinetic parameters of Saxagliptin, and sildenafil,(AUC0→∞), (AUC0→t); Cmax; tmax; t½, k; ka) will be measured using validated LC-MS/MS method. Therapeutic doses will be given to volunteers as follows: Sildenafil 50 mg single dose on day 1, then washout period from day 2 till day 8. Saxagliptin 5 mg once/day will be given from day 9 till day 12, then on day 13 the two drugs will be co-administered. Blood samples (5ml) for pharmacokinetic analysis will be collected on days 1 and 13 for Sildenafil as well as on days 12 and 13 for Saxagliptin

Study Record Dates

• First Submitted: November 14, 2019
• First Posted: November 20, 2019
• Study Start: December 1, 2019
• Primary Completion: December 30, 2019
• Study Completion: January 30, 2020
• Last Updated: November 20, 2019

Record last verified: 2019-11