Type 2 Diabetes
Conditions
Brief summary
The purpose of this study is to determine safety, efficacy and tolerability of various doses of ITCA 650 in subjects with type 2 diabetes.
Interventions
OTHERITCA 650
ITCA 650 (continuous delivery of exenatide in DUROS)
twice daily (BID) injections of exenatide commercially available Byetta: 5 mcg/dose first 12 weeks then 10 mcg/dose for 8 weeks
OTHEREx Inj/ITCA 650
twice-daily (BID) exenatide injection: 5 mcg/dose for 4 weeks then 10 mcg/dose for 8 weeks, followed by ITCA 650
Sponsors
Intarcia Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Males or females age 18-70 years * Type 2 diabetes mellitus for ≥ 6 months prior to Screening Visit 1 * On a stable (\> 3 months prior to Screening Visit 1) treatment regimen of metformin monotherapy; * Fasting plasma glucose \< 240 mg/dL at Screening Visit 1 * HbA1c ≥ 7% and ≤ 10% at Screening Visit 1
Exclusion criteria
* Prior treatment with exenatide * Treatment with any of the following antidiabetic agents within 3 months prior to Screening Visit 1: TZDs, sulfonylureas, DPP IV inhibitors, acarbose, or insulin (injected or inhaled) * History of type 1 diabetes and/or history of diabetic ketoacidosis * Body mass index ≥ 40 kg/m2; * History of organ transplantation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in HbA1c (Per Protocol) | Day 0 and Week 12 | Mean change in HbA1c over first 12 weeks (Stage I) |
| Mean Change in HbA1c (ITT) | Day 0 to Week 12 | Mean change in HbA1c through Week 12 |
Countries
United States
Participant flow
Pre-assignment details
At Stage II subjects divided into 6 total arms: ITCA 650 20 mcg/day assigned to either ITCA 650 20 mcg/day or ITCA 650 40 mcg/day; ITCA 650 40 mcg/day assigned to ITCA 650 40 mcg/day or ITCA 650 80 mcg/day; Ex Inj assigned to either ITCA 650 40 mcg/day or ITCA 650 60 mcg/day
Participants by arm
| Arm | Count |
|---|---|
| ITCA 650 20 mcg/Day- STAGE I ITCA 650 20 mcg/day continuous exenatide | 51 |
| ITCA 650 40 mcg/Day- STAGE I ITCA 650 40 mcg/day continuous exenatide | 51 |
| Exenatide Injection- STAGE I exenatide injection twice a day: 5 mcg/dose first 4 weeks then 10 mcg/dose for next 8 weeks | 53 |
| ITCA 650 20/20- STAGE II ITCA 650 20 mcg/day first 12 weeks, then ITCA 650 20 mcg/day through Week 24 | 0 |
| ITCA 650 20/60- STAGE II ITCA 650 20 mcg/day first 12 weeks then ITCA 650 60 mcg/day through Week 24 | 0 |
| ITCA 650 40/40 - STAGE II ITCA 650 40 mcg/day first 12 weeks then ITCA 650 40 mcg/day through Week 24 | 0 |
| ITCA 650 40/80 - STAGE II ITCA 650 40 mcg/day first 12 weeks then ITCA 650 80 mcg/day through Week 24 | 0 |
| Ex Inj/ITCA 650 40 mcg/Day- STAGE II Exenatide injection twice/day for 12 weeks then ITCA 650 40 mcg/day through Week 24 | 0 |
| Ex Inj/ITCA 650 60 mcg/Day- STAGE II Exenatide injection twice/day for 12 weeks then ITCA 650 60 mcg/day through Week 24 | 0 |
| ITCA 650 20/20 Continuation ITCA 650 20 mcg/day first 12 weeks then ITCA 650 through Week 48 | 0 |
| ITCA 650 20/40 Continuation ITCA 650 20 mcg/day first 12 weeks then ITCA 650 40 mcg/day through Week 48 | 0 |
| ITCA 650 40/40 Contination ITCA 650 40 mcg/day first 12 weeks then ITCA 650 40 mcg/day through Week 48 | 0 |
| ITCA 650 40/80 Continuation ITCA 650 40 mcg/day first 12 weeks then ITCA 650 80 mcg/day through Week 48 | 0 |
| Ex Inj/ITCA 650 40 Continuation Exenatide injection twice/day first 12 weeks then ITCA 650 40 mcg/day through Week 48 | 0 |
| Ex Inj/ITCA 650 60 Continuation Exenatide injection twice daily first 12 weeks then ITCA 650 60 mcg/day through Week 48 | 0 |
| Total | 155 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Stage I | A1C elevation | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Stage I | Adverse Event | 1 | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Stage I | hyperglycemia | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Stage I | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Stage I | Withdrawal by Subject | 2 | 1 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Stage II | Adverse Event | 0 | 0 | 0 | 0 | 0 | 1 | 3 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Stage II | Pregnancy | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Stage II | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Stage II Continuation | A1C elevation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Stage II Continuation | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 1 |
| Stage II Continuation | hypoglycemia | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Stage II Continuation | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 |
| Stage II Continuation | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 3 |
Baseline characteristics
| Characteristic | ITCA 650 20 mcg/Day- STAGE I | ITCA 650 40 mcg/Day- STAGE I | Exenatide Injection- STAGE I | Total |
|---|---|---|---|---|
| Age, Continuous | 54.0 years STANDARD_DEVIATION 8.3 | 53.3 years STANDARD_DEVIATION 8.9 | 53.8 years STANDARD_DEVIATION 9.6 | 53.7 years STANDARD_DEVIATION 8.9 |
| Age, Customized <=18 years | 0 participants | 0 participants | 0 participants | 0 participants |
| Age, Customized >=60 years | 10 participants | 14 participants | 14 participants | 38 participants |
| Age, Customized Between 18 and 60 years | 41 participants | 37 participants | 39 participants | 117 participants |
| Gender Female | 26 participants | 28 participants | 24 participants | 78 participants |
| Gender Male | 25 participants | 23 participants | 29 participants | 77 participants |
| Region of Enrollment United States | 51 participants | 51 participants | 53 participants | 155 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 39 / 51 | 43 / 51 | 38 / 53 | 11 / 20 | 15 / 21 | 18 / 23 | 18 / 23 | 18 / 23 | 18 / 21 | 2 / 15 | 3 / 15 | 3 / 13 | 6 / 16 | 4 / 15 | 4 / 12 |
| serious Total, serious adverse events | 1 / 51 | 0 / 51 | 0 / 53 | 1 / 20 | 1 / 21 | 2 / 23 | 2 / 23 | 0 / 23 | 0 / 21 | 0 / 15 | 1 / 15 | 1 / 13 | 2 / 16 | 0 / 15 | 0 / 12 |
Outcome results
Primary
Mean Change in HbA1c (ITT)
Mean change in HbA1c through Week 12
Time frame: Day 0 to Week 12
Population: Intent to treat analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ITCA 650 20 mcg/Day - STAGE I | Mean Change in HbA1c (ITT) | -.93 percent change | Standard Deviation 0.882 |
| ITCA 650 40 mcg/Day - STAGE I | Mean Change in HbA1c (ITT) | -0.96 percent change | Standard Deviation 0.724 |
| Exenatide Injection - STAGE I | Mean Change in HbA1c (ITT) | -0.75 percent change | Standard Deviation 0.866 |
Primary
Mean Change in HbA1c (ITT)
Mean change in HbA1c through Week 24
Time frame: Day 0 to Week 24
Population: Intent to treat analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ITCA 650 20 mcg/Day - STAGE I | Mean Change in HbA1c (ITT) | -0.89 percent change | Standard Deviation 0.66 |
| ITCA 650 40 mcg/Day - STAGE I | Mean Change in HbA1c (ITT) | -1.26 percent change | Standard Deviation 0.95 |
| Exenatide Injection - STAGE I | Mean Change in HbA1c (ITT) | -0.70 percent change | Standard Deviation 0.892 |
| ITCA 650 40/80 | Mean Change in HbA1c (ITT) | -1.36 percent change | Standard Deviation 0.664 |
| Ex Inj/ITCA 650 40 | Mean Change in HbA1c (ITT) | -1.01 percent change | Standard Deviation 0.823 |
| Ex Inj/ITCA 650 60 | Mean Change in HbA1c (ITT) | -1.51 percent change | Standard Deviation 1.266 |
Primary
Mean Change in HbA1c (ITT)
Mean change in HbA1c through Week 48
Time frame: Day 0 to Week 48
Population: Intent to treat analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ITCA 650 20 mcg/Day - STAGE I | Mean Change in HbA1c (ITT) | -1.13 percent change | Standard Deviation 0.651 |
| ITCA 650 40 mcg/Day - STAGE I | Mean Change in HbA1c (ITT) | -1.25 percent change | Standard Deviation 0.88 |
| Exenatide Injection - STAGE I | Mean Change in HbA1c (ITT) | -0.48 percent change | Standard Deviation 1.555 |
| ITCA 650 40/80 | Mean Change in HbA1c (ITT) | -1.40 percent change | Standard Deviation 0.803 |
| Ex Inj/ITCA 650 40 | Mean Change in HbA1c (ITT) | -1.16 percent change | Standard Deviation 0.988 |
| Ex Inj/ITCA 650 60 | Mean Change in HbA1c (ITT) | -1.84 percent change | Standard Deviation 1.57 |
Primary
Mean Change in HbA1c (Per Protocol)
Mean change in HbA1c over first 12 weeks (Stage I)
Time frame: Day 0 and Week 12
Population: Per protocol analysis- Only subjects with values at baseline and Week 12 endpoint are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ITCA 650 20 mcg/Day - STAGE I | Mean Change in HbA1c (Per Protocol) | -0.96 percent change | Standard Deviation 0.905 |
| ITCA 650 40 mcg/Day - STAGE I | Mean Change in HbA1c (Per Protocol) | -1.04 percent change | Standard Deviation 0.713 |
| Exenatide Injection - STAGE I | Mean Change in HbA1c (Per Protocol) | -0.82 percent change | Standard Deviation 0.87 |
Primary
Mean Change in HbA1c (Per Protocol)
Mean change in HbA1c through Week 24
Time frame: Day 0 to Week 24
Population: Per protocol analysis - Only subjects with values at baseline and Week 24 endpoint are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ITCA 650 20 mcg/Day - STAGE I | Mean Change in HbA1c (Per Protocol) | -.89 percent change | Standard Deviation 0.66 |
| ITCA 650 40 mcg/Day - STAGE I | Mean Change in HbA1c (Per Protocol) | -1.26 percent change | Standard Deviation 0.95 |
| Exenatide Injection - STAGE I | Mean Change in HbA1c (Per Protocol) | -0.67 percent change | Standard Deviation 0.908 |
| ITCA 650 40/80 | Mean Change in HbA1c (Per Protocol) | -1.36 percent change | Standard Deviation 0.664 |
| Ex Inj/ITCA 650 40 | Mean Change in HbA1c (Per Protocol) | -1.01 percent change | Standard Deviation 0.823 |
| Ex Inj/ITCA 650 60 | Mean Change in HbA1c (Per Protocol) | -1.51 percent change | Standard Deviation 1.266 |
Primary
Mean Change in HbA1c (Per Protocol)
Mean change in HbA1c through Week 48
Time frame: Day 0 to Week 48
Population: Per protocol - Only subjects with values at baseline and Week 48 endpoint are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ITCA 650 20 mcg/Day - STAGE I | Mean Change in HbA1c (Per Protocol) | -1.00 percent change | Standard Deviation 0.493 |
| ITCA 650 40 mcg/Day - STAGE I | Mean Change in HbA1c (Per Protocol) | -1.23 percent change | Standard Deviation 0.908 |
| Exenatide Injection - STAGE I | Mean Change in HbA1c (Per Protocol) | -0.69 percent change | Standard Deviation 1.182 |
| ITCA 650 40/80 | Mean Change in HbA1c (Per Protocol) | -1.37 percent change | Standard Deviation 0.837 |
| Ex Inj/ITCA 650 40 | Mean Change in HbA1c (Per Protocol) | -1.45 percent change | Standard Deviation 0.895 |
| Ex Inj/ITCA 650 60 | Mean Change in HbA1c (Per Protocol) | -1.88 percent change | Standard Deviation 1.212 |