Trial Outcomes & Findings for Efficacy and Safety of Biphasic Insulin Aspart 30 in Type 2 Diabetes Mellitus When Failing on OADs (NCT NCT00537277)

NCT ID: NCT00537277

Last Updated: 2014-12-08

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 161 participants
• Primary outcome timeframe: week 48
• Results posted on: 2014-12-08

Participant Flow

One single site in Turkey

Eligible subjects were those with type 2 diabetes inadequately controlled with oral anti-diabetic drugs (OADs) with or without basal insulin therapy.

Participant milestones

Measure	BIAsp 30 Subjects received individually adjusted dose of biphasic insulin aspart 30 (BIAsp 30) once daily for 16 weeks. If the treatment target of HbA1c below 7% was reached after 16 weeks of treatment, the subject continued the reached dose until week 48 (end of trial). If the treatment target of HbA1c below 7% was not achieved at week 16, then BIAsp 30 treatment was increased to twice daily for additional 16 weeks. If the treatment target of HbA1c below 7% was reached after 32 weeks of treatment, the subject continued the reached dose until week 48 (end of trial). If the treatment target of HbA1c below 7% was not achieved at week 32, then BIAsp 30 treatment was increased to three times daily for additional 16 weeks until week 48 (end of trial).
Overall Study STARTED	161
Overall Study Exposed to Trial Drug	160
Overall Study COMPLETED	112
Overall Study NOT COMPLETED	49

Reasons for withdrawal

Measure	BIAsp 30 Subjects received individually adjusted dose of biphasic insulin aspart 30 (BIAsp 30) once daily for 16 weeks. If the treatment target of HbA1c below 7% was reached after 16 weeks of treatment, the subject continued the reached dose until week 48 (end of trial). If the treatment target of HbA1c below 7% was not achieved at week 16, then BIAsp 30 treatment was increased to twice daily for additional 16 weeks. If the treatment target of HbA1c below 7% was reached after 32 weeks of treatment, the subject continued the reached dose until week 48 (end of trial). If the treatment target of HbA1c below 7% was not achieved at week 32, then BIAsp 30 treatment was increased to three times daily for additional 16 weeks until week 48 (end of trial).
Overall Study Adverse Event	1
Overall Study Lack of Efficacy	2
Overall Study Lost to Follow-up	12
Overall Study Protocol Violation	11
Overall Study Unclassified	4
Overall Study Inability to tolerate trial medication	4
Overall Study Non-compliance with trial procedures	15

Baseline Characteristics

Efficacy and Safety of Biphasic Insulin Aspart 30 in Type 2 Diabetes Mellitus When Failing on OADs

Baseline characteristics by cohort

Measure	BIAsp 30 n=160 Participants Subjects received individually adjusted dose of biphasic insulin aspart 30 (BIAsp 30) once daily for 16 weeks. If the treatment target of HbA1c below 7% was reached after 16 weeks of treatment, the subject continued the reached dose until week 48 (end of trial). If the treatment target of HbA1c below 7% was not achieved at week 16, then BIAsp 30 treatment was increased to twice daily for additional 16 weeks. If the treatment target of HbA1c below 7% was reached after 32 weeks of treatment, the subject continued the reached dose until week 48 (end of trial). If the treatment target of HbA1c below 7% was not achieved at week 32, then BIAsp 30 treatment was increased to three times daily for additional 16 weeks until week 48 (end of trial).
Age, Continuous	54.4 years STANDARD_DEVIATION 10.0 • n=5 Participants
Sex: Female, Male Female	98 Participants n=5 Participants
Sex: Female, Male Male	62 Participants n=5 Participants
BMI	31.1 kg/m^2 STANDARD_DEVIATION 5.7 • n=5 Participants
Diabetes Duration	9.5 years STANDARD_DEVIATION 5.1 • n=5 Participants
Height	161 cm STANDARD_DEVIATION 9.00 • n=5 Participants
Weight	80.2 kg STANDARD_DEVIATION 15.1 • n=5 Participants

PRIMARY outcome

Timeframe: week 48

Population: Full Analysis Set (FAS) was all subjects who have been exposed to at least one dose of trial drug.

Outcome measures

Measure	BIAsp 30 n=160 Participants Subjects received individually adjusted dose of biphasic insulin aspart 30 (BIAsp 30) once daily for 16 weeks. If the treatment target of HbA1c below 7% was reached after 16 weeks of treatment, the subject continued the reached dose until week 48 (end of trial). If the treatment target of HbA1c below 7% was not achieved at week 16, then BIAsp 30 treatment was increased to twice daily for additional 16 weeks. If the treatment target of HbA1c below 7% was reached after 32 weeks of treatment, the subject continued the reached dose until week 48 (end of trial). If the treatment target of HbA1c below 7% was not achieved at week 32, then BIAsp 30 treatment was increased to three times daily for additional 16 weeks until week 48 (end of trial).
Percentage of Subjects Achieving the Treatment Target of Glycosylated Haemoglobin (HbA1c) Below 7.0% Achieving treatment target HbA1c < 7.0%	34.4 percentage of subjects
Percentage of Subjects Achieving the Treatment Target of Glycosylated Haemoglobin (HbA1c) Below 7.0% Not achieving treatment target HbA1c < 7.0%	46.9 percentage of subjects

SECONDARY outcome

Timeframe: week 48

Population: Full Analysis Set (FAS) was all subjects who have been exposed to at least one dose of trial drug.

Outcome measures

Measure	BIAsp 30 n=112 Participants Subjects received individually adjusted dose of biphasic insulin aspart 30 (BIAsp 30) once daily for 16 weeks. If the treatment target of HbA1c below 7% was reached after 16 weeks of treatment, the subject continued the reached dose until week 48 (end of trial). If the treatment target of HbA1c below 7% was not achieved at week 16, then BIAsp 30 treatment was increased to twice daily for additional 16 weeks. If the treatment target of HbA1c below 7% was reached after 32 weeks of treatment, the subject continued the reached dose until week 48 (end of trial). If the treatment target of HbA1c below 7% was not achieved at week 32, then BIAsp 30 treatment was increased to three times daily for additional 16 weeks until week 48 (end of trial).
Percentage of Trial Completers Achieving the Treatment Target of Glycosylated Haemoglobin (HbA1c) Below 7.0% Achieving treatment target HbA1c < 7.0%	48.2 percentage of trial completers
Percentage of Trial Completers Achieving the Treatment Target of Glycosylated Haemoglobin (HbA1c) Below 7.0% Not achieving treatment target HbA1c < 7.0%	51.8 percentage of trial completers

SECONDARY outcome

Timeframe: weeks 0-48

Population: Safety analysis set was all subjects who have been exposed to at least one dose of trial drug.

Total number of hypoglycaemic episodes experienced from baseline (week 0) to end of trial (week 48). Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself. Minor if subject was able to treat her/himself and plasma glucose (PG) below 3.1 mmol/L or 56 mg/dL. Symptoms only if subject was able to treat her/himself and with either no PG or blood glucose measurement or PG higher than or equal to 3.1 mmol/L or 56 mg/dL.

Outcome measures

Measure	BIAsp 30 n=160 Participants Subjects received individually adjusted dose of biphasic insulin aspart 30 (BIAsp 30) once daily for 16 weeks. If the treatment target of HbA1c below 7% was reached after 16 weeks of treatment, the subject continued the reached dose until week 48 (end of trial). If the treatment target of HbA1c below 7% was not achieved at week 16, then BIAsp 30 treatment was increased to twice daily for additional 16 weeks. If the treatment target of HbA1c below 7% was reached after 32 weeks of treatment, the subject continued the reached dose until week 48 (end of trial). If the treatment target of HbA1c below 7% was not achieved at week 32, then BIAsp 30 treatment was increased to three times daily for additional 16 weeks until week 48 (end of trial).
Number of Hypoglycaemic Episodes Major	4 episodes
Number of Hypoglycaemic Episodes Minor	43 episodes
Number of Hypoglycaemic Episodes Symptom only	15 episodes

SECONDARY outcome

Timeframe: weeks 0-48

Population: Safety analysis set was all subjects who have been exposed to at least one dose of trial drug.

Total number of hypoglycaemic episodes during the day (diurnal) experienced in the trial from baseline (week 0) to end of trial (week 48). Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself. Minor if subject was able to treat her/himself and plasma glucose (PG) below 3.1 mmol/L or 56 mg/dL. Symptoms only if subject was able to treat her/himself and with either no PG or blood glucose measurement or PG higher than or equal to 3.1 mmol/L or 56 mg/dL.

Outcome measures

Measure	BIAsp 30 n=160 Participants Subjects received individually adjusted dose of biphasic insulin aspart 30 (BIAsp 30) once daily for 16 weeks. If the treatment target of HbA1c below 7% was reached after 16 weeks of treatment, the subject continued the reached dose until week 48 (end of trial). If the treatment target of HbA1c below 7% was not achieved at week 16, then BIAsp 30 treatment was increased to twice daily for additional 16 weeks. If the treatment target of HbA1c below 7% was reached after 32 weeks of treatment, the subject continued the reached dose until week 48 (end of trial). If the treatment target of HbA1c below 7% was not achieved at week 32, then BIAsp 30 treatment was increased to three times daily for additional 16 weeks until week 48 (end of trial).
Number of Diurnal Hypoglycaemic Episodes Major	2 episodes
Number of Diurnal Hypoglycaemic Episodes Minor	33 episodes
Number of Diurnal Hypoglycaemic Episodes Symptom only	13 episodes

SECONDARY outcome

Timeframe: weeks 0-48

Population: Safety analysis set was all subjects who have been exposed to at least one dose of trial drug.

Total number of hypoglycaemic episodes during the night (nocturnal) experienced in the trial from baseline (week 0) to end of trial (week 48). Hypoglycaemic episodes were defined as major, minor, or symptoms only. Major if the subject was unable to treat her/himself. Minor if subject was able to treat her/himself and plasma glucose (PG) below 3.1 mmol/L or 56 mg/dL. Symptoms only if subject was able to treat her/himself and with either no PG or blood glucose measurement or PG higher than or equal to 3.1 mmol/L or 56 mg/dL.

Outcome measures

Measure	BIAsp 30 n=160 Participants Subjects received individually adjusted dose of biphasic insulin aspart 30 (BIAsp 30) once daily for 16 weeks. If the treatment target of HbA1c below 7% was reached after 16 weeks of treatment, the subject continued the reached dose until week 48 (end of trial). If the treatment target of HbA1c below 7% was not achieved at week 16, then BIAsp 30 treatment was increased to twice daily for additional 16 weeks. If the treatment target of HbA1c below 7% was reached after 32 weeks of treatment, the subject continued the reached dose until week 48 (end of trial). If the treatment target of HbA1c below 7% was not achieved at week 32, then BIAsp 30 treatment was increased to three times daily for additional 16 weeks until week 48 (end of trial).
Number of Nocturnal Hypoglycaemic Episodes Major	2 episodes
Number of Nocturnal Hypoglycaemic Episodes Minor	10 episodes
Number of Nocturnal Hypoglycaemic Episodes Symptom only	2 episodes

SECONDARY outcome

Timeframe: weeks 0-48

Population: Safety analysis set was all subjects who have been exposed to at least one dose of trial drug.

Total number of treatment emergent SAEs experienced from baseline (week 0) to end of trial (week 48). A treatment emergent SAE were defined as an adverse event which occurred in the trial treatment period.

Outcome measures

Measure

BIAsp 30 n=160 Participants Subjects received individually adjusted dose of biphasic insulin aspart 30 (BIAsp 30) once daily for 16 weeks. If the treatment target of HbA1c below 7% was reached after 16 weeks of treatment, the subject continued the reached dose until week 48 (end of trial). If the treatment target of HbA1c below 7% was not achieved at week 16, then BIAsp 30 treatment was increased to twice daily for additional 16 weeks. If the treatment target of HbA1c below 7% was reached after 32 weeks of treatment, the subject continued the reached dose until week 48 (end of trial). If the treatment target of HbA1c below 7% was not achieved at week 32, then BIAsp 30 treatment was increased to three times daily for additional 16 weeks until week 48 (end of trial).

Number of Treatment Emergent Serious Adverse Events (SAEs)

7 events

Adverse Events

BIAsp 30

Serious events: 5 serious events

Other events: 44 other events

Deaths: 0 deaths

Serious adverse events

Measure	BIAsp 30 n=160 participants at risk Subjects received individually adjusted dose of biphasic insulin aspart 30 (BIAsp 30) once daily for 16 weeks. If the treatment target of HbA1c below 7% was reached after 16 weeks of treatment, the subject continued the reached dose until week 48 (end of trial). If the treatment target of HbA1c below 7% was not achieved at week 16, then BIAsp 30 treatment was increased to twice daily for additional 16 weeks. If the treatment target of HbA1c below 7% was reached after 32 weeks of treatment, the subject continued the reached dose until week 48 (end of trial). If the treatment target of HbA1c below 7% was not achieved at week 32, then BIAsp 30 treatment was increased to three times daily for additional 16 weeks until week 48 (end of trial).
Cardiac disorders Acute coronary syndrome	0.62% 1/160 • Number of events 1 • Adverse events were collected over a time span of 48 weeks. Safety analysis set were all subjects who have been exposed to at least one dose of trial drug.
Cardiac disorders Angina pectoris	0.62% 1/160 • Number of events 1 • Adverse events were collected over a time span of 48 weeks. Safety analysis set were all subjects who have been exposed to at least one dose of trial drug.
Cardiac disorders Coronary artery disease	0.62% 1/160 • Number of events 1 • Adverse events were collected over a time span of 48 weeks. Safety analysis set were all subjects who have been exposed to at least one dose of trial drug.
Cardiac disorders Pericardial effusion	0.62% 1/160 • Number of events 1 • Adverse events were collected over a time span of 48 weeks. Safety analysis set were all subjects who have been exposed to at least one dose of trial drug.
Endocrine disorders Toxic nodular goitre	0.62% 1/160 • Number of events 1 • Adverse events were collected over a time span of 48 weeks. Safety analysis set were all subjects who have been exposed to at least one dose of trial drug.
Metabolism and nutrition disorders Hyperglycaemia	0.62% 1/160 • Number of events 1 • Adverse events were collected over a time span of 48 weeks. Safety analysis set were all subjects who have been exposed to at least one dose of trial drug.
Respiratory, thoracic and mediastinal disorders Asphyxia	0.62% 1/160 • Number of events 1 • Adverse events were collected over a time span of 48 weeks. Safety analysis set were all subjects who have been exposed to at least one dose of trial drug.

Other adverse events

Measure	BIAsp 30 n=160 participants at risk Subjects received individually adjusted dose of biphasic insulin aspart 30 (BIAsp 30) once daily for 16 weeks. If the treatment target of HbA1c below 7% was reached after 16 weeks of treatment, the subject continued the reached dose until week 48 (end of trial). If the treatment target of HbA1c below 7% was not achieved at week 16, then BIAsp 30 treatment was increased to twice daily for additional 16 weeks. If the treatment target of HbA1c below 7% was reached after 32 weeks of treatment, the subject continued the reached dose until week 48 (end of trial). If the treatment target of HbA1c below 7% was not achieved at week 32, then BIAsp 30 treatment was increased to three times daily for additional 16 weeks until week 48 (end of trial).
Investigations Blood cholesterol increased	6.9% 11/160 • Number of events 16 • Adverse events were collected over a time span of 48 weeks. Safety analysis set were all subjects who have been exposed to at least one dose of trial drug.
Investigations Blood potassium increased	5.0% 8/160 • Number of events 12 • Adverse events were collected over a time span of 48 weeks. Safety analysis set were all subjects who have been exposed to at least one dose of trial drug.
Investigations Blood triglycerides increased	8.1% 13/160 • Number of events 18 • Adverse events were collected over a time span of 48 weeks. Safety analysis set were all subjects who have been exposed to at least one dose of trial drug.
Investigations Low density lipoprotein increased	7.5% 12/160 • Number of events 14 • Adverse events were collected over a time span of 48 weeks. Safety analysis set were all subjects who have been exposed to at least one dose of trial drug.

Additional Information

Public Access to Clinical Trials

Novo Nordisk A/S

Email: clinicaltrials@novonordisk.com

Results disclosure agreements

• Principal investigator is a sponsor employee Novo Nordisk acknowledges the Investigator's right to publish the entire results of the trial. Any such scientific paper, presentation, communication or other information concerning the investigation described in this protocol, must be submitted in writing to Novo Nordisk Trial Manager prior to submission for publication/presentation for comments. Comments will be given within four weeks from receipt of the manuscript.
• Publication restrictions are in place

Restriction type: OTHER