Interaction of Bexagliflozin With Metformin, Glimepiride and Sitagliptin
Sponsor
Theracos (Industry)
Overall Status
Completed
CT.gov ID
NCT02956044
Collaborator
(none)
54
1
9
3.9
13.7
Study Details
Study Description
Brief Summary
The purpose of this study is to examine the drug-drug interaction in your body when given the study drug, bexagliflozin, with three commonly used ant-diabetic medications, metformin, glimepiride or sitagliptin. The study will also evaluate how safe the study drug is and how well the study drug is tolerated when taken with metformin, glimepiride or sitagliptin.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
A total of 54 healthy subjects were enrolled and assigned to one of three groups of eighteen. Each group participated in one of three open-label, randomized, three treatment period, crossover studies:
-
Group 1: Bexagliflozin/metformin drug-drug interaction (DDI)
-
Group 2: Bexagliflozin/glimepiride DDI
-
Group 3: Bexagliflozin/sitagliptin DDI For each Group, every subject received a single dose of bexagliflozin tablet, 20 mg, alone, a single dose of an oral hypoglycemic agent (OHA) (1000 mg metformin, 2 mg glimepiride, or 100 mg sitagliptin) alone, and the combination of both (bexagliflozin tablet and OHA) alternately in a crossover fashion, with three treatment periods separated by a washout period of at least 7 days. Within each Group, subjects were randomized to one of six treatment sequences in an equal ratio.
To prevent hypoglycemia, subjects assigned to Group 2 (bexagliflozin/glimepiride DDI) received approximately 300 mL of a solution containing 50 g of glucose with study medication at the time of dosing, as well as approximately 75 mL of a solution containing 12.5 g of glucose every 15 minutes for 4 hours post-dose.
For each treatment period in Group 1 (bexagliflozin/metformin DDI) and Group 2 (bexagliflozin/glimepiride DDI), subjects were admitted to the clinic on the day before dosing and stayed in the clinic until 48 h post-dose. For Group 3 (bexagliflozin/sitagliptin DDI), subjects stayed in the clinic until 72 h post-dose.
For all Groups, blood samples for PK analysis were collected in each period prior to dosing (pre-dose) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, and 48 h post-dose. For Group 3, PK blood samples were also collected at 60 and 72 h post-dose. Plasma concentrations of bexagliflozin and OHAs were determined by validated liquid chromatography tandem mass spectrometry (LC MS/MS) assays.
Urine samples for PD analysis were collected in 12 h intervals. For all Groups, urine samples were collected pre-dose (-12 to 0 h) and post-dose at 0 to 12 h, 12 to 24 h, 24 to 36 h, and 36 to 48 h. For Group 3, additional samples at 48 to 60 h and 60 to 72 h post-dose were collected.
Study Design
Study Type:
Interventional
Actual Enrollment
:
54 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1, Open-label, Randomized, Three-period, Crossover Study to Evaluate Pharmacokinetic Interaction Between Bexagliflozin Tablets and Metformin, Glimepiride, or Sitagliptin in Healthy Subjects
Study Start Date
:
Nov 1, 2016
Actual Primary Completion Date
:
Mar 1, 2017
Actual Study Completion Date
:
Mar 1, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Group 1: Bexagliflozin alone
|
Drug: Bexagliflozin
Bexagliflozin tablets, 20 mg
|
| Active Comparator: Group 1: Metformin alone
|
Drug: Metformin
1000 mg metformin
|
| Active Comparator: Group 1: Bexagliflozin + Metformin
|
Drug: Bexagliflozin
Bexagliflozin tablets, 20 mg
Drug: Metformin
1000 mg metformin
|
| Active Comparator: Group 2: Bexagliflozin alone
|
Drug: Bexagliflozin
Bexagliflozin tablets, 20 mg
|
| Active Comparator: Group 2: Glimepiride alone
|
Drug: Glimepiride
4 mg glimepiride
|
| Active Comparator: Group 2: Bexagliflozin + Glimepiride
|
Drug: Bexagliflozin
Bexagliflozin tablets, 20 mg
Drug: Glimepiride
4 mg glimepiride
|
| Active Comparator: Group 3: Bexagliflozin alone
|
Drug: Bexagliflozin
Bexagliflozin tablets, 20 mg
|
| Active Comparator: Group 3: Sitagliptin alone
|
Drug: Sitagliptin
100 mg sitagliptin
|
| Active Comparator: Group 3: Bexagliflozin + Sitagliptin
|
Drug: Bexagliflozin
Bexagliflozin tablets, 20 mg
Drug: Sitagliptin
100 mg sitagliptin
|
Outcome Measures
Primary Outcome Measures
- Cmax (Maximum Observed Plasma Concentration) [Up to 72 hours]
Whole venous blood samples of 5 mL were be collected from a peripheral vein in 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 for Group 1 and 2. Pharmacokinetic (PK) blood samples were collected at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60 and 72 h post-dose for Group 3. Plasma was obtained from centrifugation, frozen and analyzed. Cmax was obtained directly from experimental observations.
- Tmax (Time of Maximum Observed Plasma Concentration) [Up to 72 hours]
Whole venous blood samples of 5 mL were collected from a peripheral vein in 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 for Group 1 and 2. PK blood samples were collected at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60 and 72 h post-dose for Group 3. Plasma was obtained from centrifugation, frozen and analyzed. Tmax was obtained directly from experimental observations.
- T1/2 (Apparent Terminal Elimination Half-life) [Up to 72 hours]
Whole venous blood samples of 5 mL were collected from a peripheral vein in 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 for Group 1 and 2. PK blood samples were collected at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60 and 72 h post-dose for Group 3. Plasma was obtained from centrifugation, frozen and analyzed. T1/2 was obtained directly from experimental observations.
- AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity) [Up to 72 hours]
Whole venous blood samples of 5 mL were collected from a peripheral vein in 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 for Group 1 and 2. PK blood samples were collected at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60 and 72 h post-dose for Group 3. Plasma was obtained from centrifugation, frozen and analyzed. AUC0-inf was estimated for each subject.
Secondary Outcome Measures
- Urinary Glucose Excretion up to 0-72 hr [up to 0-72 hr]
Pre-dose urine samples were collected from -12 to 0 h for baseline measurement. Subjects was instructed to empty their bladder prior to dosing. Post-dose urine was collected in 4 batches for Groups 1 and 2 at 0 to 12 h, 12 to 24 h, 24 o 36 h, and 36 to 48 h collections. Post-dose urine was collected in batches for Group 3 at 0 to 12 h, 12 to 24 h, 24 to 36 h, 36 to 48 h, 48 to 60 h and 60 to 72 h.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
-
Subjects with body-mass index (BMI) between 18.0 kg/m2 and 32.0 kg/m2
-
Subjects who are non-smokers for at least 3 months prior to screening
-
Subjects who are willing and able to be confined to the clinical research facility as required by the protocol
Exclusion Criteria:
-
Subjects with a clinically significant history of allergy to drugs or latex.
-
Subjects with a history of alcohol or drug dependence in the past 12 months.
-
Subjects who have donated a significant amount of blood in the past 2 months
-
Female subjects who are pregnant or breastfeeding
-
Subjects who are not willing to use an adequate form of birth control during the study and for 30 days after discharge from clinic
-
Subjects who have taken an investigational drug in the past 30 days or 7 half-lives of the investigational drug, whichever is longer
-
Subjects who had previously received anti-diabetic medication, including metformin, sitagliptin, glimepiride or drugs of the same class (i.e. biguanides, DPP-4 inhibitors or sulfonylureas), or SGLT2 inhibitors, in the past 3 months
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Clinical Research Site | Evansville | Indiana | United States | 47710 |
Sponsors and Collaborators
- Theracos
Investigators
- Study Chair: Mason Freeman, M.D., Massachusetts General Hospital
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Theracos
ClinicalTrials.gov Identifier:
NCT02956044
Other Study ID Numbers:
- THR-1442-C-453
First Posted:
Nov 4, 2016
Last Update Posted:
Jul 22, 2021
Last Verified:
Jul 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Group 1: Bexagliflozin + Metformin | Group 2: Bexagliflozin + Glimepiride | Group 3: Bexagliflozin + Sitagliptin |
|---|---|---|---|
| Arm/Group Description | Bexagliflozin tablets 20 mg alone, Metformin tablets 1000 mg alone, or Bexagliflozin 20 mg + Metformin 1000 mg | Bexagliflozin tablets 20 mg alone, Glimepiride tablets 2 mg alone, or Bexagliflozin 20 mg + Glimepiride 2 mg | Bexagliflozin tablets 20 mg alone, Sitagliptin 100 mg alone, or Bexagliflozin 20 mg + Sitagliptin 100 mg |
| Period Title: Overall Study | |||
| STARTED | 18 | 18 | 18 |
| COMPLETED | 18 | 18 | 18 |
| NOT COMPLETED | 0 | 0 | 0 |
Baseline Characteristics
| Arm/Group Title | Group 1: Bexagliflozin + Metformin | Group 2: Bexagliflozin + Glimepiride | Group 3: Bexagliflozin + Sitagliptin | Total |
|---|---|---|---|---|
| Arm/Group Description | Bexagliflozin tablets 20 mg alone, Metformin tablets 1000 mg alone, or Bexagliflozin 20 mg + Metformin 1000 mg | Bexagliflozin tablets 20 mg alone, Glimepiride tablets 2 mg alone, or Bexagliflozin 20 mg + Glimepiride 2 mg | Bexagliflozin tablets 20 mg alone, Sitagliptin 100 mg alone, or Bexagliflozin 20 mg + Sitagliptin 100 mg | Total of all reporting groups |
| Overall Participants | 18 | 18 | 18 | 54 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
42.2
(15.69)
|
37.6
(8.25)
|
43.6
(14.52)
|
41.1
(13.2)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
6
33.3%
|
5
27.8%
|
9
50%
|
20
37%
|
| Male |
12
66.7%
|
13
72.2%
|
9
50%
|
34
63%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
0
0%
|
0
0%
|
1
5.6%
|
1
1.9%
|
| Not Hispanic or Latino |
18
100%
|
18
100%
|
17
94.4%
|
53
98.1%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
5
27.8%
|
5
27.8%
|
10
55.6%
|
20
37%
|
| White |
13
72.2%
|
12
66.7%
|
8
44.4%
|
33
61.1%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
1
5.6%
|
0
0%
|
1
1.9%
|
| Weight (kg) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [kg] |
79.0
(11.75)
|
77.9
(12.37)
|
79.0
(13.21)
|
78.6
(12.23)
|
| Height (cm) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [cm] |
173.3
(9.16)
|
172.3
(6.45)
|
170.5
(8.37)
|
172.0
(8.01)
|
Outcome Measures
| Title | Cmax (Maximum Observed Plasma Concentration) |
|---|---|
| Description | Whole venous blood samples of 5 mL were be collected from a peripheral vein in 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 for Group 1 and 2. Pharmacokinetic (PK) blood samples were collected at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60 and 72 h post-dose for Group 3. Plasma was obtained from centrifugation, frozen and analyzed. Cmax was obtained directly from experimental observations. |
| Time Frame | Up to 72 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| The study was designed to evaluate the potential bexagliflozin drug interactions. Study participants were dosed with bexagliflozin alone, other drug alone or both drugs sequentially. The pharmacokinetic parameters were calculated based on the specific analyte using samples collected after dosing of the drug. Therefore, not all samples were analyzed for all outcome measurements. |
| Arm/Group Title | Group 1: Bexagliflozin Alone | Group 1: Metformin Alone | Group 1: Bexagliflozin + Metformin | Group 2: Bexagliflozin Alone | Group 2: Glimepiride Alone | Group 2: Bexagliflozin + Glimepiride | Group 3: Bexagliflozin Alone | Group 3: Sitagliptin Alone | Group 3: Bexagliflozin + Sitagliptin |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Bexagliflozin: Bexagliflozin tablets, 20 mg | Metformin: Metformin tablets, 1000 mg | Bexagliflozin: Bexagliflozin tablets, 20 mg Metformin: Metformin tablets, 1000 mg | Bexagliflozin: Bexagliflozin tablets, 20 mg | Glimepiride: Glimepiride tablets, 2 mg | Bexagliflozin: Bexagliflozin tablets, 20 mg Glimepiride: Glimepiride tablets, 2 mg | Bexagliflozin: Bexagliflozin tablets, 20 mg | Sitagliptin: Sitagliptin tablets, 100 mg | Bexagliflozin: Bexagliflozin tablets, 20 mg Sitagliptin: Sitagliptin tablets, 100 mg |
| Measure Participants | 18 | 18 | 18 | 17 | 18 | 18 | 18 | 18 | 18 |
| Bexagliflozin PK parameters |
124.6
(43.7)
|
135.5
(40.0)
|
158.6
(53.9)
|
143.7
(37.9)
|
117.1
(34.6)
|
148.3
(22.1)
|
|||
| Metformin PK parameters |
2067.6
(27.2)
|
1965.2
(33.6)
|
|||||||
| Glimepiride PK parameters |
59.9
(32.2)
|
67.1
(29.5)
|
|||||||
| Sitagliptin PK parameters |
356.6
(22.3)
|
351.2
(32.9)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Bexagliflozin Alone, Group 1: Bexagliflozin + Metformin |
|---|---|---|
| Comments | Geometric Least Square (LS) Mean was used as PK parameters | |
| Type of Statistical Test | Equivalence | |
| Comments | The acceptance range for bioequivalence is 80.0 - 125.00% | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Geometric LSM |
| Estimated Value | 108.73 | |
| Confidence Interval |
(2-Sided) 95% 94.35 to 125.30 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Confidence interval from ANOVA with treatment, period, and sequence as fixed effects, and subject as a random effect | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Metformin Alone, Group 1: Bexagliflozin + Metformin |
|---|---|---|
| Comments | Geometric LS Mean was used as PK parameters | |
| Type of Statistical Test | Equivalence | |
| Comments | The acceptance range for bioequivalence is 80.0 - 125.00% | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Geometric LSM |
| Estimated Value | 95.05 | |
| Confidence Interval |
(2-Sided) 90% 84.73 to 106.63 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Confidence interval from ANOVA with treatment, period, and sequence as fixed effects, and subject as a random effect | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Bexagliflozin Alone, Group 2: Bexagliflozin + Glimepiride |
|---|---|---|
| Comments | Geometric LS Mean was used as PK parameters | |
| Type of Statistical Test | Equivalence | |
| Comments | The acceptance range for bioequivalence is 80.0 - 125.00% | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Geometric LSM |
| Estimated Value | 89.44 | |
| Confidence Interval |
(2-Sided) 90% 70.39 to 113.65 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Confidence interval from ANOVA with treatment, period, and sequence as fixed effects, and subject as a random effect | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Glimepiride Alone, Group 2: Bexagliflozin + Glimepiride |
|---|---|---|
| Comments | Geometric LS Mean was used as PK parameters | |
| Type of Statistical Test | Equivalence | |
| Comments | The acceptance range for bioequivalence is 80.0 - 125.00% | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Geometric LSM |
| Estimated Value | 111.95 | |
| Confidence Interval |
(2-Sided) 90% 97.02 to 129.19 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Confidence interval from ANOVA with treatment, period, and sequence as fixed effects, and subject as a random effect | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Bexagliflozin Alone, Group 3: Bexagliflozin + Sitagliptin |
|---|---|---|
| Comments | Geometric LS Mean was used as PK parameters | |
| Type of Statistical Test | Equivalence | |
| Comments | The acceptance range for bioequivalence is 80.0 - 125.00% | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Geometric LSM |
| Estimated Value | 126.68 | |
| Confidence Interval |
(2-Sided) 90% 112.08 to 143.17 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Confidence interval from ANOVA with treatment, period, and sequence as fixed effects, and subject as a random effect | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Sitagliptin Alone, Group 3: Bexagliflozin + Sitagliptin |
|---|---|---|
| Comments | Geometric LS Mean was used as PK parameters | |
| Type of Statistical Test | Equivalence | |
| Comments | The acceptance range for bioequivalence is 80.0 - 125.00% | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Geometric LSM |
| Estimated Value | 98.48 | |
| Confidence Interval |
(2-Sided) 90% 84.90 to 114.23 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Confidence interval from ANOVA with treatment, period, and sequence as fixed effects, and subject as a random effect | |
| Title | Tmax (Time of Maximum Observed Plasma Concentration) |
|---|---|
| Description | Whole venous blood samples of 5 mL were collected from a peripheral vein in 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 for Group 1 and 2. PK blood samples were collected at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60 and 72 h post-dose for Group 3. Plasma was obtained from centrifugation, frozen and analyzed. Tmax was obtained directly from experimental observations. |
| Time Frame | Up to 72 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| The study was designed to evaluate the potential bexagliflozin drug interactions. Study participants were dosed with bexagliflozin alone, other drug alone or both drugs sequentially. The pharmacokinetic parameters were calculated based on the specific analyte using samples collected after dosing of the drug. Therefore, not all samples were analyzed for all outcome measurements. |
| Arm/Group Title | Group 1: Bexagliflozin Alone | Group 1: Metformin Alone | Group 1: Bexagliflozin + Metformin | Group 2: Bexagliflozin Alone | Group 2: Glimepiride Alone | Group 2: Bexagliflozin + Glimepiride | Group 3: Bexagliflozin Alone | Group 3: Sitagliptin Alone | Group 3: Bexagliflozin + Sitagliptin |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Bexagliflozin: Bexagliflozin tablets, 20 mg | Metformin: Metformin tablets, 1000 mg | Bexagliflozin: Bexagliflozin tablets, 20 mg Metformin: Metformin tablets, 1000 mg | Bexagliflozin: Bexagliflozin tablets, 20 mg | Glimepiride: Glimepiride tablets, 2 mg | Bexagliflozin: Bexagliflozin tablets, 20 mg Glimepiride: Glimepiride tablets, 2 mg | Bexagliflozin: Bexagliflozin tablets, 20 mg | Sitagliptin: Sitagliptin tablets, 100 mg | Bexagliflozin: Bexagliflozin tablets, 20 mg Sitagliptin: Sitagliptin tablets, 100 mg |
| Measure Participants | 18 | 18 | 18 | 17 | 18 | 18 | 18 | 18 | 18 |
| Bexagliflozin PK parameters |
4.0
|
3.0
|
8.0
|
6.0
|
3.0
|
4.0
|
|||
| Metformin PK parameters |
2.5
|
2.0
|
0
|
||||||
| Glimepiride PK parameters |
5.5
|
7.0
|
|||||||
| Sitagliptin PK parameters |
2.5
|
2.5
|
| Title | T1/2 (Apparent Terminal Elimination Half-life) |
|---|---|
| Description | Whole venous blood samples of 5 mL were collected from a peripheral vein in 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 for Group 1 and 2. PK blood samples were collected at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60 and 72 h post-dose for Group 3. Plasma was obtained from centrifugation, frozen and analyzed. T1/2 was obtained directly from experimental observations. |
| Time Frame | Up to 72 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| The study was designed to evaluate the potential bexagliflozin drug interactions. Study participants were dosed with bexagliflozin alone, other drug alone or both drugs sequentially. The pharmacokinetic parameters were calculated based on the specific analyte using samples collected after dosing of the drug. Therefore, not all samples were analyzed for all outcome measurements. |
| Arm/Group Title | Group 1: Bexagliflozin Alone | Group 1: Metformin Alone | Group 1: Bexagliflozin + Metformin | Group 2: Bexagliflozin Alone | Group 2: Glimepiride Alone | Group 2: Bexagliflozin + Glimepiride | Group 3: Bexagliflozin Alone | Group 3: Sitagliptin Alone | Group 3: Bexagliflozin + Sitagliptin |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Bexagliflozin: Bexagliflozin tablets, 20 mg | Metformin: Metformin tablets, 1000 mg | Bexagliflozin: Bexagliflozin tablets, 20 mg Metformin: Metformin tablets, 1000 mg | Bexagliflozin: Bexagliflozin tablets, 20 mg | Glimepiride: Glimepiride tablets, 4 mg | Bexagliflozin: Bexagliflozin tablets, 20 mg Glimepiride: Glimepiride tablets, 4 mg | Bexagliflozin: Bexagliflozin tablets, 20 mg | Sitagliptin: Sitagliptin tablets, 100 mg | Bexagliflozin: Bexagliflozin tablets, 20 mg Sitagliptin: Sitagliptin tablets, 100 mg |
| Measure Participants | 18 | 18 | 18 | 17 | 18 | 18 | 17 | 18 | 18 |
| Bexagliflozin PK parameters |
10.3
(30.4)
|
7.8
(48.6)
|
8.0
(33.3)
|
7.8
(34.4)
|
12.6
(48)
|
13.3
(38.2)
|
|||
| Metformin PK parameters |
9.0
(31.8)
|
10.2
(32.5)
|
|||||||
| Glimepiride PK parameters |
7.8
(46.8)
|
6.6
(57.8)
|
|||||||
| Sitagliptin PK parameters |
14.3
(22.3)
|
14.8
(24.5)
|
| Title | AUC0-inf (Area Under the Plasma Concentration-time Curve From Time 0 to Infinity) |
|---|---|
| Description | Whole venous blood samples of 5 mL were collected from a peripheral vein in 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 for Group 1 and 2. PK blood samples were collected at pre-dose and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 60 and 72 h post-dose for Group 3. Plasma was obtained from centrifugation, frozen and analyzed. AUC0-inf was estimated for each subject. |
| Time Frame | Up to 72 hours |
Outcome Measure Data
| Analysis Population Description |
|---|
| The study was designed to evaluate the potential bexagliflozin drug interactions. Study participants were dosed with bexagliflozin alone, other drug alone or both drugs sequentially. The pharmacokinetic parameters were calculated based on the specific analyte using samples collected after dosing of the drug. Therefore, not all samples were analyzed for all outcome measurements. |
| Arm/Group Title | Group 1: Bexagliflozin Alone | Group 1: Metformin Alone | Group 1: Bexagliflozin + Metformin | Group 2: Bexagliflozin Alone | Group 2: Glimepiride Alone | Group 2: Bexagliflozin + Glimepiride | Group 3: Bexagliflozin Alone | Group 3: Sitagliptin Alone | Group 3: Bexagliflozin + Sitagliptin |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Bexagliflozin: Bexagliflozin tablets, 20 mg | Metformin: Metformin tablets, 1000 mg | Bexagliflozin: Bexagliflozin tablets, 20 mg Metformin: Metformin tablets, 1000 mg | Bexagliflozin: Bexagliflozin tablets, 20 mg | Glimepiride: Glimepiride tablets, 2 mg | Bexagliflozin: Bexagliflozin tablets, 20 mg Glimepiride: Glimepiride tablets, 2 mg | Bexagliflozin: Bexagliflozin tablets, 20 mg | Sitagliptin: Sitagliptin tablets, 100 mg | Bexagliflozin: Bexagliflozin tablets, 20 mg Sitagliptin: Sitagliptin tablets, 100 mg |
| Measure Participants | 18 | 18 | 18 | 17 | 18 | 18 | 18 | 18 | 18 |
| Bexagliflozin PK parameters |
1154.4
(35.1)
|
1008.6
(40.2)
|
1204.9
(48.6)
|
1162.2
(47.8)
|
1011.8
(21.5)
|
1158.1
(21.9)
|
|||
| Metformin PK parameters |
13351.9
(22.5)
|
13784.6
(26.0)
|
|||||||
| Glimepiride PK parameters |
496.1
(53.3)
|
633.0
(38.5)
|
|||||||
| Sitagliptin PK parameters |
3579.6
(14.7)
|
3692.8
(16.9)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Bexagliflozin Alone, Group 1: Bexagliflozin + Metformin |
|---|---|---|
| Comments | Geometric LS Mean was used as PK parameters | |
| Type of Statistical Test | Equivalence | |
| Comments | The acceptance range for bioequivalence is 80.0 - 125.00% | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Geometric LSM |
| Estimated Value | 87.36 | |
| Confidence Interval |
(2-Sided) 90% 80.02 to 95.38 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Confidence interval from ANOVA with treatment, period, and sequence as fixed effects, and subject as a random effect | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Group 1: Metformin Alone, Group 1: Bexagliflozin + Metformin |
|---|---|---|
| Comments | Geometric LS Mean was used as PK parameters | |
| Type of Statistical Test | Equivalence | |
| Comments | The acceptance range for bioequivalence is 80.0 - 125.00% | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Geometric LSM |
| Estimated Value | 103.24 | |
| Confidence Interval |
(2-Sided) 90% 94.59 to 112.68 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Confidence interval from ANOVA with treatment, period, and sequence as fixed effects, and subject as a random effect | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Bexagliflozin Alone, Group 2: Bexagliflozin + Glimepiride |
|---|---|---|
| Comments | Geometric LS Mean was used as PK parameters | |
| Type of Statistical Test | Equivalence | |
| Comments | The acceptance range for bioequivalence is 80.0 - 125.00% | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Ratio of Geometric LSM |
| Estimated Value | 94.46 | |
| Confidence Interval |
(2-Sided) 90% 80.34 to 111.06 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Confidence interval from ANOVA with treatment, period, and sequence as fixed effects, and subject as a random effect | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Group 2: Glimepiride Alone, Group 2: Bexagliflozin + Glimepiride |
|---|---|---|
| Comments | Geometric LS Mean was used as PK parameters | |
| Type of Statistical Test | Equivalence | |
| Comments | The acceptance range for bioequivalence is 80.0 - 125.00%. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | [Ratio of Geometric LSM] |
| Estimated Value | 127.19 | |
| Confidence Interval |
(2-Sided) 90% 110.33 to 146.62 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Confidence interval from ANOVA with treatment, period, and sequence as fixed effects, and subject as a random effect | |
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Bexagliflozin Alone, Group 3: Bexagliflozin + Sitagliptin |
|---|---|---|
| Comments | Geometric LS Mean was used as PK parameters | |
| Type of Statistical Test | Equivalence | |
| Comments | The acceptance range for bioequivalence is 80.0 - 125.00% | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | [Ratio of Geometric LSM] |
| Estimated Value | 113.09 | |
| Confidence Interval |
(2-Sided) 90% 107.61 to 118.86 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Confidence interval from ANOVA with treatment, period, and sequence as fixed effects, and subject as a random effect | |
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | Group 3: Sitagliptin Alone, Group 3: Bexagliflozin + Sitagliptin |
|---|---|---|
| Comments | Geometric LS Mean was used as PK parameters | |
| Type of Statistical Test | Equivalence | |
| Comments | The acceptance range for bioequivalence is 80.0 - 125.00% | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | [Ratio of Geometric LSM] |
| Estimated Value | 103.16 | |
| Confidence Interval |
(2-Sided) 90% 99.30 to 107.17 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Other Statistical Analysis | Confidence interval from ANOVA with treatment, period, and sequence as fixed effects, and subject as a random effect | |
| Title | Urinary Glucose Excretion up to 0-72 hr |
|---|---|
| Description | Pre-dose urine samples were collected from -12 to 0 h for baseline measurement. Subjects was instructed to empty their bladder prior to dosing. Post-dose urine was collected in 4 batches for Groups 1 and 2 at 0 to 12 h, 12 to 24 h, 24 o 36 h, and 36 to 48 h collections. Post-dose urine was collected in batches for Group 3 at 0 to 12 h, 12 to 24 h, 24 to 36 h, 36 to 48 h, 48 to 60 h and 60 to 72 h. |
| Time Frame | up to 0-72 hr |
Outcome Measure Data
| Analysis Population Description |
|---|
| Only subjects with data in the specific category is analyzed |
| Arm/Group Title | Group 1: Bexagliflozin Alone | Group 1: Metformin Alone | Group 1: Bexagliflozin + Metformin | Group 2: Bexagliflozin Alone | Group 2: Glimepiride Alone | Group 2: Bexagliflozin + Glimepiride | Group 3: Bexagliflozin Alone | Group 3: Sitagliptin Alone | Group 3: Bexagliflozin + Sitagliptin |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Bexagliflozin: Bexagliflozin tablets, 20 mg | Metformin: Metformin tablets, 1000 mg | Bexagliflozin: Bexagliflozin tablets, 20 mg Metformin: Metformin tablets, 1000 mg | Bexagliflozin: Bexagliflozin tablets, 20 mg | Glimepiride: Glimepiride tablets, 4 mg | Bexagliflozin: Bexagliflozin tablets, 20 mg Glimepiride: Glimepiride tablets, 4 mg | Bexagliflozin: Bexagliflozin tablets, 20 mg | Sitagliptin: Sitagliptin tablets, 100 mg | Bexagliflozin: Bexagliflozin tablets, 20 mg Sitagliptin: Sitagliptin tablets, 100 mg |
| Measure Participants | 18 | 18 | 18 | 17 | 17 | 18 | 18 | 18 | 18 |
| 0 - 12 hours |
31.57
(8.06)
|
0.02
(0.01)
|
26.26
(8.86)
|
36.99
(14.24)
|
1.26
(4.37)
|
31.02
(11.19)
|
29.01
(6.84)
|
0.03
(0.01)
|
23.94
(7.17)
|
| 12 - 24 hours |
17.32
(11.81)
|
0.04
(0.03)
|
22.57
(8.29)
|
26.85
(9.51)
|
0.04
(0.05)
|
22.59
(11.15)
|
24.38
(7.92)
|
0.04
(0.05)
|
22.85
(9.59)
|
| 24 - 36 hours |
23.94
(9.16)
|
0.04
(0.04)
|
19.50
(8.94)
|
29.79
(10.24)
|
0.20
(0.42)
|
28.46
(11.37)
|
22.31
(8.97)
|
0.17
(0.56)
|
24.15
(9.27)
|
| 36 - 48 hours |
8.91
(4.97)
|
0.02
(0.01)
|
5.53
(4.17)
|
11.03
(7.84)
|
0.03
(0.01)
|
9.34
(7.55)
|
9.83
(6.67)
|
0.03
(0.01)
|
10.17
(5.23)
|
| 48 - 60 hours |
11.32
(8.09)
|
0.05
(0.07)
|
11.50
(7.52)
|
||||||
| 60 - 72 hours |
2.67
(3.55)
|
0.02
(0.01)
|
2.70
(2.91)
|
Adverse Events
| Time Frame | Adverse event collection began on the first clinical admission day (Day 0) and continued through D17. The subjects were actively monitored for serious adverse events for at least 14 days after discharge from the study. | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||||||||
| Arm/Group Title | Group 1: Bexagliflozin Alone | Group 1: Metformin Alone | Group 1: Bexagliflozin + Metformin | Group 2: Bexagliflozin Alone | Group 2: Glimepiride Alone | Group 2: Bexagliflozin + Glimepiride | Group 3: Bexagliflozin Alone | Group 3: Sitagliptin Alone | Group 3: Bexagliflozin + Sitagliptin | |||||||||
| Arm/Group Description | Bexagliflozin: Bexagliflozin tablets, 20 mg | Metformin: Metformin tablets, 1000 mg | Bexagliflozin: Bexagliflozin tablets, 20 mg Metformin: Metformin tablets, 1000 mg | Bexagliflozin: Bexagliflozin tablets, 20 mg | Glimepiride: Glimepiride tablets, 2 mg | Bexagliflozin: Bexagliflozin tablets, 20 mg Glimepiride: Glimepiride tablets, 2 mg | Bexagliflozin: Bexagliflozin tablets, 20 mg | Sitagliptin: Sitagliptin tablets, 100 mg | Bexagliflozin: Bexagliflozin tablets, 20 mg Sitagliptin: Sitagliptin tablets, 100 mg | |||||||||
All Cause Mortality |
||||||||||||||||||
| Group 1: Bexagliflozin Alone | Group 1: Metformin Alone | Group 1: Bexagliflozin + Metformin | Group 2: Bexagliflozin Alone | Group 2: Glimepiride Alone | Group 2: Bexagliflozin + Glimepiride | Group 3: Bexagliflozin Alone | Group 3: Sitagliptin Alone | Group 3: Bexagliflozin + Sitagliptin | ||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/18 (0%) | 0/18 (0%) | 0/18 (0%) | 0/18 (0%) | 0/18 (0%) | 0/18 (0%) | 0/18 (0%) | 0/18 (0%) | 0/18 (0%) | |||||||||
Serious Adverse Events |
||||||||||||||||||
| Group 1: Bexagliflozin Alone | Group 1: Metformin Alone | Group 1: Bexagliflozin + Metformin | Group 2: Bexagliflozin Alone | Group 2: Glimepiride Alone | Group 2: Bexagliflozin + Glimepiride | Group 3: Bexagliflozin Alone | Group 3: Sitagliptin Alone | Group 3: Bexagliflozin + Sitagliptin | ||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/18 (0%) | 0/18 (0%) | 0/18 (0%) | 0/18 (0%) | 0/18 (0%) | 0/18 (0%) | 0/18 (0%) | 0/18 (0%) | 0/18 (0%) | |||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||||
| Group 1: Bexagliflozin Alone | Group 1: Metformin Alone | Group 1: Bexagliflozin + Metformin | Group 2: Bexagliflozin Alone | Group 2: Glimepiride Alone | Group 2: Bexagliflozin + Glimepiride | Group 3: Bexagliflozin Alone | Group 3: Sitagliptin Alone | Group 3: Bexagliflozin + Sitagliptin | ||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/18 (16.7%) | 11/18 (61.1%) | 13/18 (72.2%) | 6/18 (33.3%) | 2/18 (11.1%) | 4/18 (22.2%) | 3/18 (16.7%) | 1/18 (5.6%) | 2/18 (11.1%) | |||||||||
| Gastrointestinal disorders | ||||||||||||||||||
| Diarrhea | 0/18 (0%) | 0 | 9/18 (50%) | 9 | 7/18 (38.9%) | 7 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 |
| Nausea | 0/18 (0%) | 0 | 3/18 (16.7%) | 3 | 2/18 (11.1%) | 2 | 2/18 (11.1%) | 2 | 1/18 (5.6%) | 1 | 3/18 (16.7%) | 3 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 |
| Dyspepsia | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 2/18 (11.1%) | 2 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 |
| Abdominal pain | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 |
| Abdominal pain upper | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 |
| Vomiting | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 2/18 (11.1%) | 2 | 1/18 (5.6%) | 1 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 |
| Flatulence | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 |
| General disorders | ||||||||||||||||||
| Tenderness | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 |
| Vessel puncture site haemorrhage | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 |
| Puncture site pain | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 |
| Puncture site swelling | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 |
| Fatigue | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 |
| Xerosis | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 |
| Catheter site induration | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 |
| Catheter site pain | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||||||||
| Gun shot wound | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||||||||
| Hypoglycemia | 2/18 (11.1%) | 2 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 3/18 (16.7%) | 3 | 0/18 (0%) | 0 | 0/18 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||
| Arthralgia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 |
| Nervous system disorders | ||||||||||||||||||
| Headache | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 4/18 (22.2%) | 4 | 4/18 (22.2%) | 4 | 1/18 (5.6%) | 1 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 |
| Dizziness | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 |
| Paresthesia | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||||||||||||
| Dysmenorrhea | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||||||||||||||
| Dermatitis contact | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 |
| Ecchymosis | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 |
| Swelling of face | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 |
| Urticaria | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 1/18 (5.6%) | 1 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 | 0/18 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Program Director |
|---|---|
| Organization | Translational Medicine Group |
| Phone | 617-726-4236 |
| yhalvorsen@ccib.mgh.harvard.edu |
Responsible Party:
Theracos
ClinicalTrials.gov Identifier:
NCT02956044
Other Study ID Numbers:
- THR-1442-C-453
First Posted:
Nov 4, 2016
Last Update Posted:
Jul 22, 2021
Last Verified:
Jul 1, 2021