Trial Outcomes & Findings for Long-term Study of Alogliptin as an Add-on to Rapid-Acting Insulin Secretagogues in Type 2 Diabetes (NCT NCT01456130)

Last Updated: 2014-04-21

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

67 participants

Primary outcome timeframe

52 Weeks

Results posted on

2014-04-21

Participant Flow

Participants took part in the study at 14 investigative sites in Japan from 10 November 2011 to 16 March 2013.

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.

Participant milestones

Participant milestones
Measure	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.
Overall Study STARTED	67
Overall Study COMPLETED	57
Overall Study NOT COMPLETED	10

Reasons for withdrawal

Reasons for withdrawal
Measure	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.
Overall Study Adverse Event	4
Overall Study Voluntary Withdrawal	1
Overall Study Lack of Efficacy	4
Overall Study Other	1

Baseline Characteristics

Long-term Study of Alogliptin as an Add-on to Rapid-Acting Insulin Secretagogues in Type 2 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Alogliptin n=67 Participants 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.
Age, Continuous	61.6 years STANDARD_DEVIATION 10.52 • n=5 Participants
Age, Customized < 65 years	37 participants n=5 Participants
Age, Customized ≥ 65 years	30 participants n=5 Participants
Sex: Female, Male Female	26 Participants n=5 Participants
Sex: Female, Male Male	41 Participants n=5 Participants
Weight	66.64 kg STANDARD_DEVIATION 14.409 • n=5 Participants
Height	161.7 cm STANDARD_DEVIATION 10.22 • n=5 Participants
Body Mass Index (BMI)	25.38 kg/m^2 STANDARD_DEVIATION 4.347 • n=5 Participants
Duration of Diabetes	7.44 years STANDARD_DEVIATION 5.872 • n=5 Participants
Glycosylated Hemoglobin (HbA1c)	7.63 percent glycosylated hemoglobin STANDARD_DEVIATION 0.957 • n=5 Participants
Baseline hemoglobin A1c (HbA1c) categories < 6.5 %	3 participants n=5 Participants
Baseline hemoglobin A1c (HbA1c) categories ≥ 6.5 and < 7.0%	17 participants n=5 Participants
Baseline hemoglobin A1c (HbA1c) categories ≥ 7.0 and < 8.0%	25 participants n=5 Participants
Baseline hemoglobin A1c (HbA1c) categories ≥ 8.0%	22 participants n=5 Participants
Fasting blood glucose	182.1 mg/dL STANDARD_DEVIATION 45.07 • n=5 Participants
Fasting blood glucose categories < 130 mg/dL	6 participants n=5 Participants
Fasting blood glucose categories ≥ 130 to < 160 mg/dL	17 participants n=5 Participants
Fasting blood glucose categories ≥ 160 mg/dL	44 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Alogliptin n=67 Participants 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.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Any adverse event	57 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Adverse event leading to discontinuation	5 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Serious adverse event (SAE)	6 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) SAE leading to discontinuation	0 participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Death	0 participants

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: Full analysis set: All randomized participants who received at least one dose of double-blind study medication.

The change in the value of glycosylated hemoglobin collected at Week 52 or at the final visit relative to Baseline.

Outcome measures

Outcome measures
Measure	Alogliptin n=67 Participants 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.
Change From Baseline in Glycosylated Hemoglobin (HbA1c)	-0.46 percentage of glycosylated hemoglobin Interval -0.69 to 0.221

SECONDARY outcome

Timeframe: Week 52

Population: Full analysis set

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.

Outcome measures

Outcome measures
Measure	Alogliptin n=67 Participants 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.
Percentage of Participants With a Clinical Response HbA1c of < 5.8%	4.5 percentage of participants Interval 0.933 to 12.533
Percentage of Participants With a Clinical Response HbA1c of < 6.5%	28.4 percentage of participants Interval 18.015 to 40.691

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: Full analysis set.

The change in the value of fasting glucose collected at Week 52 or the final visit relative to Baseline.

Outcome measures

Outcome measures
Measure	Alogliptin n=67 Participants 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.
Change From Baseline in Fasting Glucose	-10.5 mg/dL Interval -18.75 to -2.3

Adverse Events

Alogliptin

Serious events: 6 serious events

Other events: 57 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Alogliptin n=67 participants at risk 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.
Infections and infestations Bronchiolitis	1.5% 1/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute lymphocytic leukaemia	1.5% 1/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Cardiac disorders Myocardial infarction	1.5% 1/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Duodenal ulcer	1.5% 1/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Inguinal hernia	1.5% 1/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Back pain	1.5% 1/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Other adverse events

Other adverse events
Measure	Alogliptin n=67 participants at risk 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.
Infections and infestations Nasopharyngitis	35.8% 24/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Bronchitis	6.0% 4/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Cellulitis	3.0% 2/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Gastroenteritis	3.0% 2/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Gingivitis	3.0% 2/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Influenza	3.0% 2/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Oral herpes	3.0% 2/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Periodontitis	3.0% 2/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Blood and lymphatic system disorders Anaemia	3.0% 2/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Immune system disorders Seasonal allergy	4.5% 3/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Hyperuricaemia	3.0% 2/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Insomnia	3.0% 2/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Sleep disorder	3.0% 2/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Headache	4.5% 3/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Eye disorders Asthenopia	4.5% 3/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Eye disorders Cataract	3.0% 2/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Eye disorders Conjunctivitis allergic	3.0% 2/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Eye disorders Diabetic retinopathy	3.0% 2/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract inflammation	11.9% 8/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Constipation	7.5% 5/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Dental caries	6.0% 4/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Gastrooesophageal reflux disease	6.0% 4/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Abdominal pain upper	3.0% 2/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Eczema	3.0% 2/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Skin and subcutaneous tissue disorders Rash	3.0% 2/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Arthralgia	7.5% 5/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Back pain	6.0% 4/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders Diabetic nephropathy	6.0% 4/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Chest pain	3.0% 2/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
General disorders Malaise	3.0% 2/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Gamma-glutamyltransferase increased	3.0% 2/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Arthropod sting	3.0% 2/67 • 52 weeks At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Additional Information

Medical Director, Clinical Science

Takeda

Phone: 800-778-2860

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Publication restrictions are in place

Restriction type: OTHER