A Phase 3, Randomized, Active Comparator, Double-Blind, Multi-Center Study to Compare the Efficacy, Safety and Tolerability of ITCA 650 to Sitagliptin as Add-on Therapy to Metformin in Patients with Type 2 Diabetes. ITCA 650-CLP-105
This is a Phase 3, multi-center, randomized, active comparator, double-blind, study to be conducted in approximately 330 sites globally. approximately 500 patients will be randomized 1:1 to treatment with iTCa 650 or sitagliptin. Patients will be treated for 52 weeks.
in this double-blind study approximately 500 patients on metformin monotherapy will be randomized 1:1 to one of two groups:
* Group 1: iTCa 650 60 mcg/day following an introductory dose of iTCa 650 20 mcg/day, plus once-daily oral placebo
* Group 2: sitagliptin 100 mg/day plus iTCa placebo
efficacy and safety of iTCa 650 versus sitagliptin will be studied during a 52-week Treatment
Period. The study device (iTCa 650 or iTCa placebo) will be placed on Day 0, replaced at
Weeks 13 and 39 and removed at Week 52. in addition, each patient will take either daily oral
sitagliptin (100 mg) or daily placebo.
Group 1 will initially be treated with iTCa 650 20 mcg/day for 13 weeks. after 13 weeks
iTCa 650 20 mcg/day will be replaced with iTCa 650 60 mcg/day for 26 weeks. at Week 39
the iTCa 650 60 mcg/day device will be replaced with a new iTCa 650 60 mcg/day device.
at Week 52, the iTCa 650 device will be removed. in addition, Group 1 patients will take
once-daily oral placebo for the duration of the treatment period.
Group 2 will take oral sitagliptin (100 mg) once-daily for the duration of the treatment period.
Group 2 patients will also have an iTCa placebo device placed for 13 weeks. after 13 weeks
the iTCa placebo will be replaced with a new iTCa placebo device for 26 weeks. at Week 39
the iTCa placebo device will be replaced with a new iTCa placebo device. The iTCa
placebo device will be removed at Week 52.
Patients will be maintained throughout the 52-week treatment period on the dose of metformin
they were taking at randomization.
Patients experiencing loss of glycemic control (persistent hyperglycemia) will be prescribed
rescue therapy and continued in the study for safety evaluation.
Final database lock will occur following collection and cleaning of all patient data for the
duration of the 52-week Treatment Period and following finalization of the Statistical analysis
Plan. Complete statistical analyses will be performed and the study will be unblinded.
1. Understanding of the study procedures and agreement to participate in the
study by giving written informed consent at or prior to Screening;
2. Men or women age 18 to 80 years, inclusive;
3. Diagnosis of type 2 diabetes for >=3 months prior to Screening;
4. On a stable (>=3 months prior to Screening) treatment regimen of metformin
monotherapy 1500 mg/day. Patients must be willing to increase the dose of
metformin to 2 grams daily at Screening. If the patient cannot tolerate the increase in metformin dose to 2 grams daily during screening, they may be down titrated to their previous dose prior to Randomization as long as it is at least 1500mg/day. If it has been previously
documented that the subject cannot tolerate a higher dose of metformin
than 1500 mg/day, s[Single Quote]he may participate as long as they are taking
metformin at a dose of at least 1500 mg/day;
5. Agreement to maintain the same dose of metformin from Randomization to the
end of the study;
6. HbA1c >=7.5% and <=10.5% at Screening. One re-test of this parameter is
allowed prior to randomization;
7. Stable body weight (not varying by >10% for 3 months before Screening);
8. Calcitonin <50 ng/L (50 pg/mL) at Screening;
9. Body mass index (BMI) >=25 kg/m2 and <=45 kg/m2 at Screening;
10. Women may be enrolled if all of the following criteria (in addition to other
criteria) are met:
* they are not pregnant,
* they are not breast feeding, and
* they do not plan on becoming pregnant during the study;
11. Women of childbearing potential (WOCBP) must have a negative
pregnancy test at Screening. Women are considered to be of childbearing
potential unless they meet one of the following criteria as documented by
* they have had a hysterectomy or tubal ligation prior to signing the
informed consent form, or
* they are post-menopausal, defined for women <=50 years old as
>=2 years since their last menstrual period, and for women >50 years
old as >=1 year since their last menstrual period or have a folliclestimulating
hormone (FSH) level in the menopausal range;
12. WOCBP must agree to use an adequate method of contraception during the
study and for one additional menstrual cycle following the ET Visit. Women
practicing abstinence or whose partner(s) is (are) sterile should be
considered to be of childbearing potential. Adequate methods of
contraception for WOCBP include: oral, implanted or injectable
contraceptive hormones; mechanical products (e.g., IUD); or barrier
methods (e.g., diaphragm, condoms, cervical cap) with spermicide. The
patient[Single Quote]s understanding of this requirement must be documented by the