臨床研究等提出・公開システム

Treatment Preference for Weekly Dipeptidyl Peptidase-4 (DPP-4) Inhibitors Versus Daily DPP-4 Inhibitors in Patients With Type 2 Diabetes Mellitus

Public Title Treatment Preference for Weekly DPP-4 Inhibitors Versus Daily DPP-4 Inhibitors in Participants With Type 2 Diabetes Mellitus (TRINITY)

60

Demographic and other baseline characteristics were similar between groups.

A total of 60 participants signed the informed consent form. All participants met the eligibility criteria for randomization into the treatment period of the study. Overall, 30 participants were randomized to the T-A group and 30 participants were randomized to the A-T group. All participants in the T-A group completed the planned study treatment. Two participants in the A-T group did not complete the planned study treatment (pretreatment event/AE, n = 1; and other, n = 1).

Eight patients in the trelagliptin group (13.6%; 8/59 patients) and four patients in the alogliptin group (6.7%; 4/60 participants) experienced a treatment-emergent AE (TEAE), the majority of which were mild in intensity. One patient (1.7%) in each group experienced a TEAE of moderate intensity. One patient (1.7%) in the trelagliptin group experienced two serious TEAEs that led to study drug discontinuation. Examination of this patients' intestinal obstruction revealed colon cancer, both of which resulted in trelagliptin discontinuation in the A-T group. Infections and infestations were the most common non-serious TEAE by SOC in the trelagliptin and alogliptin group, experienced by six patients (10.2%) and three patients (5.0%), respectively. Two patients (3.4%) in the trelagliptin group, and one patient (1.7%) in the alogliptin group experienced a viral upper respiratory tract infection. Two patients (3.4%) in the trelagliptin group only experienced an upper respiratory tract infection. No deaths were reported during this study. No drug-related TEAEs or drug-related serious AEs were reported during this study. Conclusions: Trelagliptin 100 mg and alogliptin 25 mg were well-tolerated and no new safety signals were identified.

At 16 weeks, patients expressed a significantly higher treatment preference for alogliptin (51.7%, n = 31) than trelagliptin (30.0%, n = 18) in both groups combined (T-A and A-T) (Mainland-Gart test, p=0.0141). In the T-A group alone, 60.0% of patients preferred alogliptin, and 26.7% of patients preferred trelagliptin. In the A-T group alone, 43.3% and 33.3% of patients preferred alogliptin and trelagliptin, respectively. At 16 weeks, patients who received at least one dose of both trelagliptin and alogliptin also expressed a significantly higher treatment preference for alogliptin (50.8%) than trelagliptin (30.5%) in both groups combined (T-A and A-T) (Mainland-Gart test, p=0.0231). In the T-A group alone, 60.0% of patients preferred alogliptin and 26.7% of patients preferred trelagliptin. In the A-T group alone, 41.4% and 34.5% of patients preferred alogliptin and trelagliptin, respectively.

At 16 weeks, treatment preference by background factors (demographic and baseline characteristics) revealed a greater preference for alogliptin than trelagliptin in both groups combined (T-A and A-T), which support the results of the primary endpoint. Conclusions: At the end of the 16-week study, patients expressed a significantly higher treatment preference for once-daily alogliptin 25 mg than once-weekly trelagliptin 100 mg. Treatment satisfaction after 8 weeks was numerically higher in the alogliptin, and trelagliptin group compared with baseline. Additionally, HbA1c in both treatment groups was comparable to baseline.

The decision to administer once-weekly or once-daily DPP-4 inhibitor treatment is likely to depend on patient preference, patient-physician discussions (i.e., patientcentered communications), and the treatment practices of the treating physician. Refer to conclusions of "Adverse Events" and "Secondary Outcome Measures" sections for the rest of the summary.

Yes

Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

Takeda Pharmaceutical Company Limited

https://www.takeda.com/jp/who-we-are/contact-us/

-

Takeda Pharmaceutical Company Limited

https://www.takeda.com/jp/who-we-are/contact-us/

+81-6-6204-2111

-

completed

Aug. 18, 2017

Interventional

Randomized, open-label, two-way crossover

treatment purpose

4

1. Participants who have been diagnosed with type 2 diabetes mellitus.
2. Participants who are being treated with any of the following DPP-4 inhibitors for at least 8 weeks prior to the time of informed consent (Week 0).
- Sitagliptin : 50 mg once daily
- Alogliptin : 25 mg once daily
- Linagliptin : 5 mg once daily
- Teneligliptin : 20 mg once daily
- Saxagliptin : 5 mg once daily
3. Participants who were judged by the investigators possible to change the treatment from daily dosing of DPP-4 inhibitor shown in Inclusion Criteria 2 to study drug trelagliptin 100 mg or alogliptin 25 mg.
4. Participants whose glycosylated hemoglobin (HbA1c) value measured within 8 weeks prior to the time of informed consent (Week 0) is below 10.0%.
5. Participants who responded to Diabetes Treatment Satisfaction Questionnaire (DTSQ) at the time of informed consent (Week 0).
6. Participants who were judged by the investigators capable to understand the contents of this clinical research and comply with them.
7. Participants who are able to sign and date the Informed Consent Form before any clinical research procedure begins.
8. Participants who are at least 20 years old at the time of giving the consent.
9. Participants who are classified as outpatients.

1. Participants who have a history of taking once-weekly dosing of DPP-4 inhibitor (trelagliptin or omarigliptin).
2. Participants who are being treated with drugs other than those for once-daily oral dosing for the purpose of treatment of chronic complication (for example, "BENET Tablets 75 mg", a therapeutic agent for osteoporosis which is administered once monthly).
3. Participants who are being treated with twice-daily dosing of DPP-4 inhibitor (vildagliptin or anagliptin).
4. Participants who are being treated with anti-diabetic fixed-dose combination pill contained a DPP-4 inhibitor.
5. Participants with moderate or severe renal impairment (for example, participant whose estimated glomerular filtration rate (eGFR) is below 60 mL/min/1.73m^2).
6. Participants for whom blood sugar control by insulin preparations is desired (for example, participants with severe ketosis, diabetic coma or precoma, type 1 diabetes mellitus, severe infection, or serious trauma before or after surgery).
7. Participants who have a history of hypersensitivity or allergy to DPP-4 inhibitor.
8. Participants with serious heart disease, cerebrovascular disorder, or participants with serious disease in the pancreas, blood, etc.
9. Participants with unstable proliferative diabetic retinopathy.
10. Participants with malignant tumor.
11. Participants who are pregnant, breast-feeding, possibly pregnant, or planning to become pregnant.
12. Participants participating in other clinical studies.
13. Participants who have been determined as inappropriate participants by the investigator.

Both

Type 2 diabetes mellitus

investigational material(s)
Generic name etc : Trelagliptin 100 mg + Alogliptin 25 mg
INN of investigational material : Trelagliptin, Alogliptin
Therapeutic category code : 396 Antidiabetic agents
Dosage and Administration for Investigational material : Trelagliptin preceding group (T-A group): Trelagliptin 100 mg, tablets, orally, once a week for 8 weeks, followed by alogliptin, 25 mg, tablets, orally, once a day for 8 weeks.
Generic name etc : Alogliptin 25 mg + Trelagliptin 100 mg
INN of investigational material : Alogliptin, Trelagliptin
Therapeutic category code : 396 Antidiabetic agents
Dosage and Administration for Investigational material : Alogliptin preceding group (A-T group): Alogliptin, 25 mg, tablets, orally, once a day for 8 weeks, followed by trelagliptin, 100 mg, tablets, orally, once a week for 8 weeks.

control material(s)
Generic name etc : -
INN of investigational material : -
Therapeutic category code :
Dosage and Administration for Investigational material : -

efficacy
Number of Participants by their Treatment Preference Using Standardized Questions at the End of Treatment Period
Time Frame: At Week 16
Participants answered standardized questions about their preference of drug therapy for Type 2 Diabetes Mellitus. Participants selected one choice from the following 4 choices; either once-weekly DPP-4 inhibitor or daily DPP-4 inhibitor, once-weekly DPP-4 inhibitor, daily DPP-4 inhibitor, neither once-weekly DPP-4 inhibitor nor daily DPP-4 inhibitor. Reported data was the number of participants with a choice of either trelagliptin (a once-weekly DPP-4 inhibitor) or alogliptin (a once-daily DPP-4 inhibitor), trelagliptin, alogliptin, neither trelagliptin nor alogliptin.

efficacy
Number of Participants by their Treatment Preference Using Standardized Questions at the End of Treatment Period by Background Factors
Time Frame: At Week 16
Participants answered standardized questions about their preference of drug therapy for Type 2 Diabetes Mellitus. The preference of drug therapy was categorized by background factors like age (years), gender, height (cm), weight (kg), BMI (kg/m^2), duration of diabetes (years), work status, alcohol intake history, smoking habits, experience of educational hospitalization on DM, presence of cohabiter, percentage of compliance with DPP-4 inhibitors during 4-weeks before the start of treatment period, number of oral drugs per day at the beginning of treatment period (excluding investigational drug), complication of metabolic syndrome, percentage of HbA1c (NGSP is the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at the time of informed consent.

efficacy
Number of Participants by their Treatment Preference Using Standardized Questions at the End of Treatment Period by Background Factors (T-A Administered Group)
Time Frame: At Week 16
Participants answered standardized questions about their preference of drug therapy for Type 2 Diabetes Mellitus. The preference of drug therapy was categorized by background factors like age (years), gender, height (cm), weight (kg), BMI (kg/m^2), duration of diabetes (years), work status, alcohol intake history, smoking habits, experience of educational hospitalization on DM, presence of cohabiter, percentage of compliance with DPP-4 inhibitors during 4-weeks before the start of treatment period, number of oral drugs per day at the beginning of treatment period (excluding investigational drug), complication of metabolic syndrome, percentage of HbA1c (NGSP is the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at the time of informed consent.

efficacy
Number of Participants by their Treatment Preference Using Standardized Questions at the End of Treatment Period by Background Factors (A-T Administered Group)
Time Frame: At Week 16
Participants answered standardized questions about their preference of drug therapy for Type 2 Diabetes Mellitus. The preference of drug therapy was categorized by background factors like age (years), gender, height (cm), weight (kg), BMI (kg/m^2), duration of diabetes (years), work status, alcohol intake history, smoking habits, experience of educational hospitalization on DM, presence of cohabiter, percentage of compliance with DPP-4 inhibitors during 4-weeks before the start of treatment period, number of oral drugs per day at the beginning of treatment period (excluding investigational drug), complication of metabolic syndrome, percentage of HbA1c (NGSP is the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) at the time of informed consent.

-

Aug. 05, 2017