Phase 1 Bioavailability Study of SYR-322MET

Healthy Volunteers Clinical Trial

Official title:

An Open-Label, Single-dose, Randomized, Crossover Study to Determine the Bioavailability and Bioequivalence of Alogliptin 12.5 mg and Metformin 1000 mg When Administered as Individual Tablets and as a Fixed-Dose Combination Tablet Vipdomet (Alogliptin FDC With Metformin) in Russian Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02508168
• Other study ID #: SYR-322MET-1003
• Secondary ID: U1111-1168-6473
• Status: Completed
• Phase: Phase 1
• First received: July 23, 2015
• Last updated: October 4, 2016
• Start date: April 2016
• Est. completion date: April 2016

Study information

• Verified date: October 2016
• Source: Takeda
• Contact: n/a
• Is FDA regulated: No
• Health authority: Russia: The Ministry of Health of the Russian Federation
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine the relative bioavailability of alogliptin 12.5 milligram (mg) and immediate-release metformin 1000 mg when administered as individual tablets and as a fixed-dose combination (FDC) product.

Description:

The drug being tested in this study is called SYR-322MET (alogliptin 12.5 mg and metformin 1000 mg FDC tablet). SYR-322MET is being tested to assess whether its pharmacokinetic properties (how it is processed by the body) are affected when administered as a FDC compared to administration of alogliptin and metformin alone. This study will look at lab results in people who take SYR-322MET.

This crossover study will enroll approximately 24 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of two treatment sequences. All participants will receive both treatments over two periods; the order of receipt will be determined by the randomization code. All participants will receive the following study medications by the end of the study:

• Alogliptin 12.5 mg + Metformin 1000 mg as individual tablets

• SYR-322MET (alogliptin 12.5 mg and metformin 1000 mg fixed-dose combination [FDC] tablet)

This single center trial will be conducted in Russia. The overall time to participate in this study is up to 63 days. Participants will make multiple visits to the clinic including two 4-day periods of confinement to the clinic, and will be contacted by telephone 14 days after last dose of study drug for a follow-up assessment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

1. In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.

2. Signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures including requesting that a participant fast for any laboratory evaluations.

3. Is a healthy male or female.

4. Is aged 18 to 55 years, inclusive, at the time of informed consent and first study medication dose.

5. Weighs at least 50 kilogram (kg) and has a body mass index (BMI) from 18.5 to 30.0 kilogram per square meter (kg/m^2), inclusive at Screening.

6. A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 30 days after last dose.

7. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent and throughout the duration of the study and for 30 days after last dose.

Exclusion Criteria

1. Has received any investigational compound within 30 days prior to Check-in (Day-1).

2. Has received alogliptin or metformin hydrochloride (HCl) in a previous clinical study or as a therapeutic agent within 90 days prior to Check-in (Day-1).

3. Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in the conduct of this study (example, spouse, parent, child, sibling) or may consent under duress.

4. Has clinically significant history or current diagnosis of cardiovascular, respiratory, neurological, endocrine, hematopoietic, immune, urinary, genital, gastrointestinal, hepatic and psychiatric diseases.

5. Has fasting blood glucose lower than 3.88 millimoles per liter (mmol/L)

6. Has experienced acute infectious diseases within 4 weeks before screening.

7. Has a history of clinically significant allergic reactions or has a known hypersensitivity to any component of the formulation of alogliptin, metformin or related compounds.

8. Has a positive urine drug result for drugs of abuse (defined as any illicit drug use) or positive alcohol breath test at Screening or Check-in (Day -1).

9. Consumes over 10 drinks weekly (1 drink is equivalent to 0.5 liters of beer, 200 milliliter [mL] of dry wine or 50 mL of hard liquor) or has a history of alcoholism, drug and/or substance abuse.

10. Has taken any excluded medication, supplements, or food products during the time periods listed in the Excluded Medications and Dietary Products table, including intake of medicines with pronounced effects on blood circulation, liver function (barbiturates, omeprazole, cimetidine, etc.) within 2 months before Day -1 of Period 1.

11. If female, the participant is pregnant or lactating or intending to become pregnant before, during, or within 30 days after participating in this study; or intending to donate ova during such time period.

12. If male, the participant intends to donate sperm during the course of this study or for 12 weeks after the last dose of study medication.

13. If female, the subject is having unprotected sex with non-sterilized men within 30 days before the IMP administration.

14. Has current or recent (within 6 months) gastrointestinal disease that would be expected to influence the absorption of drugs (that is, a history of malabsorption, esophageal reflux, peptic ulcer disease, erosive esophagitis, frequent [more than once per week] occurrence of heartburn, or any surgical intervention.

15. Has non-standard diet (example, vegetarian or vegan) or lifestyle (including nighttime work, extreme physical activity such as weights lifting), which may interfere with the trial.

16. Has a history of cancer, except basal cell carcinoma which has been in remission for at least 5 years prior to Day 1 of Period 1.

17. Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antibody or syphilis at screening.

18. Has used nicotine-containing products (including but not limited to cigarettes, pipes, cigars, chewing tobacco, nicotine patch or nicotine gum) within 28 days prior to Check-in Day -1. Cotinine test is positive at Screening or Check-in (Day 1).

19. Has poor peripheral venous access.

20. Has donated or lost 450 mL or more of his or her blood volume (including plasmapheresis), or had a transfusion of any blood product within 30 days prior to Day 1 of Period 1.

21. Has abnormalities in routine physician examination, laboratory and/or ECG findings

22. Has a systolic blood pressure greater (>)130 millimeter of mercury (mm Hg) or less than (<)100 mm Hg , diastolic blood pressure >90 mm Hg or <70 mm Hg; heart rate <60 bpm or >80 bpm at screening (Day -28 to Day -2) or check-in to Period 1 (Day -1).

23. Has participated in any clinical study within 3 months before Day -1 of Period 1.

Study Design

Allocation: Randomized, Endpoint Classification: Bio-availability Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Alogliptin
Alogliptin 12.5 mg tablets
• Metformin Hydrochloride
Metformin hydrochloride 1000 mg tablets
• SYR-322MET
SYR-322MET (alogliptin 12.5 mg and metformin 1000 mg) fixed-dose combination (FDC) tablets

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Takeda

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Alogliptin	(AUC(0-tlqc) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUC[0-tlqc]).	Day 1 predose and at multiple time points (up to 72 hours) post-dose.	No
Primary	Cmax: Maximum Observed Plasma Concentration for Alogliptin	Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.	Day 1 predose and at multiple time points (up to 72 hours) post-dose.	No
Primary	AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Metformin	(AUC(0-tlqc) is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration (AUC[0-tlqc]).	Day 1 predose and at multiple time points (up to 72 hours) post-dose.	No
Primary	Cmax: Maximum Observed Plasma Concentration for Metformin	Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.	Day 1 predose and at multiple time points (up to 72 hours) post-dose.	No
Secondary	Percentage of Participants who Experience at Least one Post-dose Adverse Event (AE)	An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (example, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug.	Day 1 of Period 1 up to 30 days after the last dose of study medication (up to 38 days)	Yes
Secondary	Percentage of Participants who Meet the Markedly Abnormal Criteria for Safety Laboratory Tests at Least Once Post Dose	Standard safety laboratory values (hematology and chemistry) will be collected throughout study and compared to pre-specified criteria for markedly abnormal values.	At Day 4 and Day 7 of Period 2	Yes
Secondary	Percentage Of Participants who Meet the Markedly Abnormal Criteria for Vital Sign Measurements at Least Once Post Dose	Vital sign measurements will be collected throughout study and compared to pre-specified criteria for markedly abnormal values.	Day 1 up to Day 4 of each period	Yes
Secondary	Percentage of Participants who Meet the Markedly Abnormal Criteria for Safety Electrocardiogram (ECG) Parameters at Least Once Post Dose	Standard 12-lead ECG measurements will be collected throughout the study and compared to pre-specified criteria for markedly abnormal values.	At Day 1 and Day 4 of each period	Yes