Type2 Diabetes MellitusPhase 1NCT03167411
Bexagliflozin Drug/Drug Interaction Study With Exenatide Injection
A Phase 1 study testing Bexagliflozin and Exenatide Injection in people with Type2 Diabetes Mellitus, run by Theracos at 1 site in United States.
Trial summary
The purpose of this study is to examine the drug-drug interaction when given the study drug, bexagliflozin, with one of the most commonly prescribed glucagon-like peptide 1 receptor agonist (GLP-1 RA) exenatide. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Type2 Diabetes Mellitus
- What is being tested?
- Bexagliflozin and Exenatide Injection
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 24 May 2017to 29 Jun 2017
- 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 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male and female subjects who were between the ages of 18 and 65 years, inclusive, in good health based on medical history, physical examination, electrocardiogram and routine laboratory tests.
- Subjects with body-mass index (BMI) between 18.0 kg/m2 and 32.0 kg/m2, inclusive.
- Subjects who were non-smokers for at least 3 months prior to screening.
- Subjects with adequate venous access at multiple sites in both arms.
- Subjects who were willing and able to be confined to the clinical research facility as required by the protocol.
- Subjects who had the ability to comprehend and who were willing to provide written informed consent in accordance with institutional and regulatory guidelines.
Who cannot join
- Subjects who were determined by the investigator or sub-investigator to be unsuitable for participation in the study based on medical conditions or factors that would have influenced adherence to study activities.
- Subjects with a clinically significant history of allergy to drugs or latex.
- Subjects with a history of hypoglycemia.
- Subjects with a history of alcohol or drug dependence in the last 12 months.
- Subjects who donated 400 mL of whole blood within 56 days, 200 mL of whole blood within one month, or donated blood components within 14 days of screening.
- Subjects who used prescription or over-the-counter (OTC) drugs within 14 days prior to the first dose.
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- Subjects who used vitamin preparations or supplements (including St. John's Wort and ginseng) within 14 days prior to the first dose .
- Subjects who were not willing to refrain from smoking, alcohol, grapefruit, grapefruit juice or related products, caffeine consumption (including chocolate), and strenuous exercise within 72 h prior to Day 1 and through the end of the PK study.
- Male subjects who did not agree to refrain from donating sperm and use appropriate birth control methods including condoms with spermicide, female partner's use of diaphragm with spermicide, or stable oral, implanted, or injected contraceptive hormones, or with an intrauterine device, or female partner is surgically sterile (i.e. have undergone partial or full hysterectomy, or bilateral oophorectomy) or postmenopausal (absence of menses greater than 12 months and age >45 years), for a period of 30 days after discharge from the clinic.
- Female subjects of childbearing potential who were not willing to use an adequate method of contraception including bilateral tubal ligation, intrauterine device, diaphragm with spermicide and male partner's use of male condom with spermicide, and to not become pregnant for the duration of the study. Female subjects who were surgically sterile (partial or full hysterectomy, or bilateral oophorectomy) or postmenopausal (absence of menses greater than 12 months and age >45 years) were eligible if they tested negative on the pregnancy test.
- Subjects who had been treated with an investigational drug within 30 days or 7 half-lives of the investigational drug, whichever is longer, prior to the first dose of study drug in this trial.
- Subjects who had previously received exenatide, or any other GLP-1 RAs within three months from the screening or subjects who had had any GLP-1 RA and suffered an adverse reaction due to the medication.
- Subjects who had previously received bexagliflozin, or any other SGLT2 inhibitors within 3 months from the screening.
- Subjects whose screening ECG demonstrates any one of the following: heart rate >100 bpm, QRS >120 msec, QTc >470 msec (corrected by Fridericia's formula), PR >220 msec (a subject with PR >220 msec was generally to be excluded but exceptions may have been allowed at the discretion of the investigator), or any clinically significant arrhythmia.
- Subjects whose sitting blood pressure was above 140/90 mmHg at screening. If the sitting blood pressure at screening was above 140/90 mmHg, one repeat measurement was allowed and the subject may have been randomized if the blood pressure was 140/90 +/-5 mm Hg at the discretion of the Investigator.
- Subjects who had a positive result of hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, urinary drug or urinary cotinine test.
- Subjects with human immunodeficiency virus (HIV) infection.
- Subjects who had had a febrile illness within 5 days prior to the first dose of study medication.
- Subjects vaccinated within 30 days (with the exception of the flu vaccine) prior to the first dose of investigational drug.
- Subjects with a history of acute or chronic pancreatitis or gall stones.
- Positive urine glucose at screening.
- Subjects with estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m2 or a history of kidney transplant.
- Subjects with digestion problems, including gastroesophageal reflux disease, irritable bowel syndrome, gastroparesis, and any other disorder deemed by the investigator to be clinically significant.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Open-label, Randomized, Two-period, Two-treatment, Crossover Study to Evaluate the Effect of Exenatide on the Pharmacokinetics and Pharmacodynamics of Bexagliflozin in Healthy Subjects
The purpose of this study is to examine the drug-drug interaction when given the study drug, bexagliflozin, with one of the most commonly prescribed glucagon-like peptide 1 receptor agonist (GLP-1 RA) exenatide. The study will also evaluate how safe the study drug is and how well the study drug is tolerated when administered with exenatide injection.
Read the detailed description
This was a phase 1, single center, open-label, 2 × 2 crossover study designed to assess the effects of exenatide injection on the PK and PD of orally administered bexagliflozin tablets. Healthy subjects were randomly assigned to one of two groups with 10 subjects per group. Each group received both the treatments, alternately, in a crossover fashion with the two treatment periods separated by a 7-day washout period.
In Treatment Period 1, subjects were admitted to the clinic on day 0, the day before dosing, and stayed in the clinic until 48 h post-dose. After an overnight fast of at least 10 h, subjects in Group 1 received a single oral dose of bexagliflozin tablets, 20 mg, alone 30 min before breakfast, and subjects in Group 2 received a subcutaneous (SC) injection of exenatide at 10 µg twice a day (bid) with an initial dose 30 min prior to a single oral dose of bexagliflozin tablets, 20 mg, and 1 hr before breakfast, followed by the second dose of exenatide alone 1 hr prior to the evening meal.
In Treatment Period 2, subjects were admitted to the clinic on day 7, the day before dosing, and stayed in the clinic until 48 hr post-dose. After an overnight fast of at least 10 h, subjects in Group 1 received a SC injection exenatide at 10 µg bid with an initial dose 30 min prior to a single oral dose of bexagliflozin tablets, 20 mg, and 1 hr before breakfast and followed by the second dose of exenatide alone 1 hr prior to the evening meal. Subjects in Group 2 received a single oral dose of bexagliflozin tablets, 20 mg, alone 30 minutes before breakfast.
Blood samples for bexagliflozin plasma concentration were collected during each period at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 hr post-dose. Pre-dose urine samples were collected from -12 to 0 hr for baseline measurement of PD parameters. Post-dose urine samples were collected in four batches: 0 to 12 hr, 12 to 24 hr, 24 to 36 hr, and 36 to 48 hr.
Clinical laboratory tests and safety monitoring were conducted during both treatment periods for each group.
- Conditions
- Type2 Diabetes Mellitus
- Being tested
- Bexagliflozin, Exenatide Injection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BexagliflozinDrug
Bexagliflozin tablets, 20 mg
Exenatide InjectionDrug
Also called Byetta®
Byetta® (Exenatide), 10 ug, bid, subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| Bexagliflozin alone | Experimental | Not described Receives: Drug: Bexagliflozin |
| Bexagliflozin with exenatide injection | Active comparator | Not described Receives: Drug: Bexagliflozin; Drug: Exenatide Injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cmax (Maximum Observed Plasma Concentration)
Whole venous blood samples of 3 mL was collected from peripheral vein at each period at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36 and 48 h post-dose of bexagliflozin. A non-compartmental pharmacokinetic analysis was used to calculate the PK parameters. Cmax was obtained directly from experimental observations.
Measured: Up to 48 hrs
Tmax (Time of Maximum Observed Plasma Concentration)
Whole venous blood samples of 3 mL was collected from peripheral vein at each period at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36 and 48 h post-dose of bexagliflozin. A non-compartmental pharmacokinetic analysis was used to calculate the PK parameters. Tmax was obtained directly from experimental observations.
Measured: Up to 48 hrs
T1/2 (Apparent Terminal Elimination Half-life)
Whole venous blood samples of 3 mL was collected from peripheral vein at each period at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36 and 48 h post-dose of bexagliflozin. A non-compartmental pharmacokinetic analysis was used to calculate the PK parameters. T1/2 was calculated as the natural log of 2 divided by the terminal phase rate constant.
Measured: Up to 48 hrs
AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity)
Whole venous blood samples of 3 mL was collected from peripheral vein at each period at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36 and 48 h post-dose of bexagliflozin. A non-compartmental pharmacokinetic analysis was used to calculate the PK parameters. AUC0-inf was calculated using the linear trapezoidal rule, using actual elapsed time values. If the actual time of sample collection was not available, the nominal time was used for the purpose of parameter estimation.
Measured: Up to 48 hrs
Secondary outcomes (1)
Urinary Glucose Excretion (UGE)
Post-dose urine was collected without preservative in four batches: 0 to 12 h, 12 to 24 h, 24 to 36 h, and 36 to 48 h collections. After collection, the total volume of each batch and collection time was recorded. UGE, including UGE(t1-t2) and total 0-24 h and 0-48 h UGE were calculated. UGE(t1-t2) was derived from urine volume (Vt1-t2) multiplied by glucose concentration divided by 100.
Measured: 0-48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2017
- Study start24 May 2017
- Primary completion29 Jun 2017
- Study completion29 Jun 2017
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 Type2 Diabetes MellitusStudies 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
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Theracos
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Mason Freeman, M.D., Study chair, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03167411
- Sponsor's protocol ID
- THR-1442-C-458
- Status last verified
- Mar 2021
- First submitted
- 24 May 2017
- Last updated
- 28 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- 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 28 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-label, Randomized, Two-period, Two-treatment, Crossover Study to Evaluate the Effect of Exenatide on the Pharmacokinetics and Pharmacodynamics of Bexagliflozin in Healthy Subjects
- ClinicalTrials.gov ID
- NCT03167411
- Acronym / sponsor ID
- THR-1442-C-458
- Conditions
- Type2 Diabetes Mellitus
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- TheracosIndustry (pharma, biotech, devices)
- Study start
- 24 May 2017 (actual)
- Primary completion
- 29 Jun 2017 (actual)
- Study completion
- 29 Jun 2017 (actual)
- First posted
- 30 May 2017 (actual)
- Results
- Posted 28 May 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to examine the drug-drug interaction when given the study drug, bexagliflozin, with one of the most commonly prescribed glucagon-like peptide 1 receptor agonist (GLP-1 RA) exenatide. The study will also evaluate how safe the study drug is and how well the study drug is tolerated when administered with exenatide injection.
Detailed description
This was a phase 1, single center, open-label, 2 × 2 crossover study designed to assess the effects of exenatide injection on the PK and PD of orally administered bexagliflozin tablets. Healthy subjects were randomly assigned to one of two groups with 10 subjects per group. Each group received both the treatments, alternately, in a crossover fashion with the two treatment periods separated by a 7-day washout period.
In Treatment Period 1, subjects were admitted to the clinic on day 0, the day before dosing, and stayed in the clinic until 48 h post-dose. After an overnight fast of at least 10 h, subjects in Group 1 received a single oral dose of bexagliflozin tablets, 20 mg, alone 30 min before breakfast, and subjects in Group 2 received a subcutaneous (SC) injection of exenatide at 10 µg twice a day (bid) with an initial dose 30 min prior to a single oral dose of bexagliflozin tablets, 20 mg, and 1 hr before breakfast, followed by the second dose of exenatide alone 1 hr prior to the evening meal.
In Treatment Period 2, subjects were admitted to the clinic on day 7, the day before dosing, and stayed in the clinic until 48 hr post-dose. After an overnight fast of at least 10 h, subjects in Group 1 received a SC injection exenatide at 10 µg bid with an initial dose 30 min prior to a single oral dose of bexagliflozin tablets, 20 mg, and 1 hr before breakfast and followed by the second dose of exenatide alone 1 hr prior to the evening meal. Subjects in Group 2 received a single oral dose of bexagliflozin tablets, 20 mg, alone 30 minutes before breakfast.
Blood samples for bexagliflozin plasma concentration were collected during each period at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 hr post-dose. Pre-dose urine samples were collected from -12 to 0 hr for baseline measurement of PD parameters. Post-dose urine samples were collected in four batches: 0 to 12 hr, 12 to 24 hr, 24 to 36 hr, and 36 to 48 hr.
Clinical laboratory tests and safety monitoring were conducted during both treatment periods for each group.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Bexagliflozin alone | Experimental | Drug: Bexagliflozin |
| Bexagliflozin with exenatide injection | Active comparator | Drug: Bexagliflozin, Drug: Exenatide Injection |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male and female subjects who were between the ages of 18 and 65 years, inclusive, in good health based on medical history, physical examination, electrocardiogram and routine laboratory tests.
- Subjects with body-mass index (BMI) between 18.0 kg/m2 and 32.0 kg/m2, inclusive.
- Subjects who were non-smokers for at least 3 months prior to screening.
- Subjects with adequate venous access at multiple sites in both arms.
- Subjects who were willing and able to be confined to the clinical research facility as required by the protocol.
Key exclusion criteria (23 listed)
- Subjects who were determined by the investigator or sub-investigator to be unsuitable for participation in the study based on medical conditions or factors that would have influenced adherence to study activities.
- Subjects with a clinically significant history of allergy to drugs or latex.
- Subjects with a history of hypoglycemia.
- Subjects with a history of alcohol or drug dependence in the last 12 months.
- Subjects who donated 400 mL of whole blood within 56 days, 200 mL of whole blood within one month, or donated blood components within 14 days of screening.
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 |
|---|---|---|
| BexagliflozinBexagliflozin tablets, 20 mg | Drug | Bexagliflozin alone, Bexagliflozin with exenatide injection |
| Exenatide InjectionAlso: Byetta®Byetta® (Exenatide), 10 ug, bid, subcutaneous injection | Drug | Bexagliflozin with exenatide injection |
Primary outcome
Cmax (Maximum Observed Plasma Concentration)
Time frame: Up to 48 hrs
Whole venous blood samples of 3 mL was collected from peripheral vein at each period at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36 and 48 h post-dose of bexagliflozin. A non-compartmental pharmacokinetic analysis was used to calculate the PK parameters. Cmax was obtained directly from experimental observations.
Tmax (Time of Maximum Observed Plasma Concentration)
Time frame: Up to 48 hrs
Whole venous blood samples of 3 mL was collected from peripheral vein at each period at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36 and 48 h post-dose of bexagliflozin. A non-compartmental pharmacokinetic analysis was used to calculate the PK parameters. Tmax was obtained directly from experimental observations.
T1/2 (Apparent Terminal Elimination Half-life)
Time frame: Up to 48 hrs
Whole venous blood samples of 3 mL was collected from peripheral vein at each period at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36 and 48 h post-dose of bexagliflozin. A non-compartmental pharmacokinetic analysis was used to calculate the PK parameters. T1/2 was calculated as the natural log of 2 divided by the terminal phase rate constant.
AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity)
Time frame: Up to 48 hrs
Whole venous blood samples of 3 mL was collected from peripheral vein at each period at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36 and 48 h post-dose of bexagliflozin. A non-compartmental pharmacokinetic analysis was used to calculate the PK parameters. AUC0-inf was calculated using the linear trapezoidal rule, using actual elapsed time values. If the actual time of sample collection was not available, the nominal time was used for the purpose of parameter estimation.
1 secondary outcome
Urinary Glucose Excretion (UGE)
Time frame: 0-48 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2021.
- 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.
Mason Freeman, M.D. study chair
Massachusetts General Hospital
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 Bexagliflozin and Exenatide Injection in people with Type2 Diabetes Mellitus, run by Theracos at 1 site in United States.
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 6 inclusion and 23 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 28 May 2021. 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 United States. 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 28 May 2021). 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?
Cmax (Maximum Observed Plasma Concentration) (time frame: Up to 48 hrs). The study lists 4 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 28 May 2021.