Diabetes Mellitus
Conditions
Brief summary
The purpose of this study is to evaluate the safety and efficacy of alogliptin as an add-on to a rapid-acting insulin secretagogue (medicine that stimulates insulin release) in type 2 diabetic patients with inadequate blood glucose control despite treatment with a rapid-acting insulin secretagogue as well as diet and exercise therapies.
Detailed description
One alogliptin 25 mg tablet was orally administered once daily before breakfast for up to 52 weeks. The dose of alogliptin was adjusted according to the severity of the participant's renal dysfunction based on serum creatinine (SCr) levels. Participants with moderate renal dysfunction (SCr, \>1.4 - ≤2.4 mg/dL for men and \>1.2 - ≤ 2.0 mg/dL for women) received alogliptin 12.5 mg tablets.
Interventions
DRUGAlogliptin
Alogliptin tablets
DRUGRapid-acting insulin secretagogue
Either of the following commercially available rapid-acting insulin secretagogues as prescribed by the Investigator: (i) Nateglinide: Dose: 30 mg tablet or 90 mg tablet (ii) Mitiglinide calcium hydrate: Dose: 5 mg tablet or 10 mg tablet
Sponsors
Takeda
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosed with type 2 diabetes mellitus. 2. Had an HbA1c of ≥ 6.5% and \< 10.0% at the start of the observation period (Week -2). 3. Had been receiving specific diet and exercise (if applicable) therapies since at least 10 weeks prior to the start of the observation period (Week -2). 4. Had been receiving basic diabetes treatment with a rapid-acting insulin secretagogue (nateglinide or mitiglinide calcium hydrate) alone using a stable dosage regimen since at least 10 weeks prior to the start of the observation period (Week -2). 5. Was suitable for combination therapy of either of the above rapid-acting insulin secretagogues (nateglinide or mitiglinide calcium hydrate) and another antidiabetic drug at the start of the observation period (Week -2) in the investigator's or subinvestigator's opinion. 6. Participants complicated by hypertension had stable blood pressure control and needed neither dose adjustment of the ongoing antihypertensive (including discontinuation and interruption) nor additional use of another antihypertensive throughout the duration of the study in the investigator's or subinvestigator's opinion. 7. Male or female and aged 20 years or older at the time of signing of informed consent. 8. If female, and of child-bearing potential and sexually active with a nonsterilized male partner agreed to use adequate contraception routinely from signing of informed consent throughout the duration of the study. 9. Visited the study site on an outpatient basis during the observation period. 10. Was capable of understanding and complying with protocol requirements in the investigator's or subinvestigator's opinion. 11. Signed and dated the informed consent documents prior to the start of any study procedures.
Exclusion criteria
1. Severe renal dysfunction or end-stage renal disease \[e.g., a serum creatinine (SCr) level of \>2.4 mg/dL (men) or \>2.0 mg/dL (women) at the start of the observation period (Week -2)\]. 2. Obvious clinical manifestations of hepatic impairment \[e.g., an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) value of ≥ 2.5 times the upper limit of normal at the start of the observation period (Week -2)\]. 3. Any serious cardiac disease, serious cerebrovascular disorder, or serious pancreatic or hematological disease (e.g., requiring hospitalization for treatment). 4. Systolic blood pressure of ≥ 180 mmHg or diastolic blood pressure of ≥ 110 mmHg during the observation period. 5. A condition requiring insulin for blood glucose control (e.g., a patient with severe ketosis, diabetic coma or precoma, type 1 diabetes mellitus, severe infection, a pre- or post-operative condition, or serious trauma). 6. Malignant tumor. 7. History of hypersensitivity or allergies to dipeptidyl-peptidase-4 (DPP-4) inhibitors. 8. A habitual drinker whose daily alcohol consumption was \>100 mL on average. 9. A history of drug abuse (defined as any illicit drug use) or alcohol abuse. 10. Required to take excluded medications during the duration of the study. 11. Previously received SYR-322 or Nesina® Tablets in a clinical study or as a therapeutic drug. 12. Received any investigational product (including investigational products for postmarketing clinical studies) within 12 weeks prior to the start of the observation period. 13. Had participated in another clinical study at signing of informed consent. 14. If female, was pregnant or lactating, or intended to become pregnant between signing of informed consent and 1 month after the end of the study; or intended to donate ova during such time period. 15. A study site employee, an immediate family member of a study site employee or in a dependent relationship with a study site employee who was involved in the conduct of this study (e.g., spouse, parent, child, sibling), or might consent under duress. 16. Changed the dosing regimen of the ongoing rapid-acting insulin secretagogue during the observation period. 17. History of hypersensitivity or allergies to rapid-acting insulin secretagogues. 18. Any condition for which Nesina® Tablets, nateglinide, or mitiglinide calcium hydrate was contraindicated as defined in their package inserts. 19. Otherwise ineligible for participation in the study in the investigator's or subinvestigator's opinion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) | 52 Weeks | An TEAE is any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have a causal relationship with this treatment. A serious TEAE is defined as any untoward medical occurrence that resulted in death, was life threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability or incapacity, led to a congenital anomaly/birth defect or was an important medical event that may have required intervention to prevent any of items above. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) | Baseline and Week 52 | The change in the value of glycosylated hemoglobin collected at Week 52 or at the final visit relative to Baseline. |
| Percentage of Participants With a Clinical Response | Week 52 | Clinical response is defined as an HbA1c level less than 5.8% or less than 6.5% at Week 52 or at the final visit. |
| Change From Baseline in Fasting Glucose | Baseline and Week 52 | The change in the value of fasting glucose collected at Week 52 or the final visit relative to Baseline. |
Countries
Japan
Participant flow
Recruitment details
Participants took part in the study at 14 investigative sites in Japan from 10 November 2011 to 16 March 2013.
Pre-assignment details
Patients with type 2 diabetes with inadequate blood glucose control despite treatment with a rapid-acting insulin secretagogue as well as diet and exercise therapies were enrolled in a single treatment group.
Participants by arm
| Arm | Count |
|---|---|
| Alogliptin Alogliptin 25 mg (or 12.5 mg for participants with moderate renal dysfunction) tablets, orally once daily and a rapid-acting insulin secretagogue as prescribed by the Investigator for up to 52 weeks. | 67 |
| Total | 67 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Lack of Efficacy | 4 |
| Overall Study | Other | 1 |
| Overall Study | Voluntary Withdrawal | 1 |
Baseline characteristics
| Characteristic | Alogliptin |
|---|---|
| Age, Continuous | 61.6 years STANDARD_DEVIATION 10.52 |
| Age, Customized < 65 years | 37 participants |
| Age, Customized ≥ 65 years | 30 participants |
| Baseline hemoglobin A1c (HbA1c) categories < 6.5 % | 3 participants |
| Baseline hemoglobin A1c (HbA1c) categories ≥ 6.5 and < 7.0% | 17 participants |
| Baseline hemoglobin A1c (HbA1c) categories ≥ 7.0 and < 8.0% | 25 participants |
| Baseline hemoglobin A1c (HbA1c) categories ≥ 8.0% | 22 participants |
| Body Mass Index (BMI) | 25.38 kg/m^2 STANDARD_DEVIATION 4.347 |
| Duration of Diabetes | 7.44 years STANDARD_DEVIATION 5.872 |
| Fasting blood glucose | 182.1 mg/dL STANDARD_DEVIATION 45.07 |
| Fasting blood glucose categories < 130 mg/dL | 6 participants |
| Fasting blood glucose categories ≥ 130 to < 160 mg/dL | 17 participants |
| Fasting blood glucose categories ≥ 160 mg/dL | 44 participants |
| Glycosylated Hemoglobin (HbA1c) | 7.63 percent glycosylated hemoglobin STANDARD_DEVIATION 0.957 |
| Height | 161.7 cm STANDARD_DEVIATION 10.22 |
| Sex: Female, Male Female | 26 Participants |
| Sex: Female, Male Male | 41 Participants |
| Weight | 66.64 kg STANDARD_DEVIATION 14.409 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 57 / 67 |
| serious Total, serious adverse events | 6 / 67 |
Outcome results
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
An TEAE is any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have a causal relationship with this treatment. A serious TEAE is defined as any untoward medical occurrence that resulted in death, was life threatening, required or prolonged inpatient hospitalization, resulted in persistent or significant disability or incapacity, led to a congenital anomaly/birth defect or was an important medical event that may have required intervention to prevent any of items above.
Time frame: 52 Weeks
Population: Safety analysis set - All participants who received at least one dose of the investigational product (alogliptin) and a rapid-acting insulin secretagogue.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alogliptin | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Adverse event leading to discontinuation | 5 participants |
| Alogliptin | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Any adverse event | 57 participants |
| Alogliptin | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Serious adverse event (SAE) | 6 participants |
| Alogliptin | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | SAE leading to discontinuation | 0 participants |
| Alogliptin | Number of Participants With Treatment Emergent Adverse Events (TEAEs) | Death | 0 participants |
Secondary
Change From Baseline in Fasting Glucose
The change in the value of fasting glucose collected at Week 52 or the final visit relative to Baseline.
Time frame: Baseline and Week 52
Population: Full analysis set.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Alogliptin | Change From Baseline in Fasting Glucose | -10.5 mg/dL |
Secondary
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
The change in the value of glycosylated hemoglobin collected at Week 52 or at the final visit relative to Baseline.
Time frame: Baseline and Week 52
Population: Full analysis set: All randomized participants who received at least one dose of double-blind study medication.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Alogliptin | Change From Baseline in Glycosylated Hemoglobin (HbA1c) | -0.46 percentage of glycosylated hemoglobin |
Secondary
Percentage of Participants With a Clinical Response
Clinical response is defined as an HbA1c level less than 5.8% or less than 6.5% at Week 52 or at the final visit.
Time frame: Week 52
Population: Full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alogliptin | Percentage of Participants With a Clinical Response | HbA1c of < 5.8% | 4.5 percentage of participants |
| Alogliptin | Percentage of Participants With a Clinical Response | HbA1c of < 6.5% | 28.4 percentage of participants |