Evaluation of Drug Interactions of Saxagliptin With Sildenafil in Healthy Volunteers

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.

Study Overview

• Status: Unknown
• Conditions: Diabetes Mellitus, Type 2; Drug Interaction; Erectile Dysfunction With Diabetes Mellitus
• Intervention / Treatment: Drug: Saxagliptin 5mg; Drug: Sildenafil 50 mg

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Not Applicable

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Age 18-45 years.
2. Ideal weight within the normal range according to accepted life tables.
3. Non-contributory history and normal physiological examination.
4. Laboratory data within normal limits.
5. Performance and compliance.
6. The subjects should be without known history of alcohol or drug abuse problems and should preferably be non-smokers.
7. 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).

Exclusion Criteria:

1. A known hypersensitivity to the drug.
2. Gastrointestinal diseases.
3. Auto immune diseases.
4. Renal diseases or dysfunction.
5. Cardiovascular disease of any type.
6. Pancreatic disease including diabetes.
7. Hepatic disease.
8. Hematological, osteopathic, or pulmonary disease.
9. History of alcoholism or drug abuse.
10. Serious Psychological illness.
11. Positive HIV-I.
12. Smoking (if including they should be identified).
13. Abnormal (out of range) laboratory values.
14. Subject who have taken any medication (Rx or OTC) less than two weeks of the trials starting date.
15. 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.
16. Any prior surgery of the gastrointestinal tract that may interfere with drug absorption.
17. Treatment with any known enzyme-inducing / inhibiting agents within 30 days prior to the start of the study and throughout the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy volunteer; 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; Saxagliptin 5mg oral tablet; Other Names: Onglyza; Drug: Sildenafil 50 mg; Sildenafil 50 mg Oral Tablet; Other Names: Viagra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Ain Shams University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2019
• Primary Completion (Anticipated): December 30, 2019
• Study Completion (Anticipated): January 30, 2020

Study Registration Dates

• First Submitted: November 14, 2019
• First Submitted That Met QC Criteria: November 19, 2019
• First Posted (Actual): November 20, 2019

Study Record Updates

• Last Update Posted (Actual): November 20, 2019
• Last Update Submitted That Met QC Criteria: November 19, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Sexual Dysfunctions, Psychological; Sexual Dysfunction, Physiological; Diabetes Mellitus; Diabetes Mellitus, Type 2; Erectile Dysfunction; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Phosphodiesterase Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate; Saxagliptin
• Other Study ID Numbers: 57

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No