Comparing Patient-adjusted Versus Physician-adjusted Titr... | NCT01589653

ID	Type	Description	Link
U1111-1125-7572	Other Identifier	WHO

Status Module

Oversight Module

Label	Type	Description	Intervention Names
Subject-driven titration	Experimental		Drug: biphasic insulin aspart 30
Investigator-driven titration	Experimental		Drug: biphasic insulin aspart 30

Name	Type	Description	Arm Group Labels	Other Names
biphasic insulin aspart 30	Drug	Dose individually adjusted by the subjects themselves according to the titration algorithm every second week. Administered subcutaneously (s.c., under the skin) twice daily.

Outcomes Module

Measure	Description	Time Frame
Change in HbA1c From Baseline	Change in HbA1c (%) from baseline to the end of the treatment period.	Week 0, week 20

Secondary Outcomes

Measure	Description	Time Frame
Change in Fasting Plasma Glucose (FPG) (Laboratory Values) From Baseline	Change in FPG (laboratory values) from baseline to the end of the treatment period	Week 0, week 20
Number of Hypoglycaemic Episodes During the Trial From Baseline

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Diagnosed with type 2 diabetes for a minimum of 12 months prior to screening
Currently treated with a NPH insulin for at least 3 months prior to screening
Stable treatment (no change in dose or regimen) with a total daily dose of at least 1500 mg metformin or maximum tolerated dose (minimum 1000 mg) ± additional OAD treatment. The metformin treatment must have been stable for at least 2 months prior to screening
HbA1c between 7.0% and 10.0% (both inclusive). (One re-test within one week of screening visit is allowed. The last sample will be conclusive.)
Body Mass Index (BMI) below or equal to 40.0 kg/m^2
Able and willing to eat at least 2 main meals each day during the trial
Able and willing to adhere to the protocol including compliance with performance of self measured plasma glucose (SMPG), injection regimen and titrating themselves according to the protocol
Experience in performing self-measured plasma glucose (SMPG)

Exclusion Criteria:

Treatment with any thiazolidinedione (TZD) and Glucagon-like peptide-1 (GLP-1) receptor agonists or pramlintide within the last 3 months prior to screening
Impaired hepatic function defined as alanine aminotransferase (ALAT) above or equal to 2.5 times upper referenced limit. (One re-test within one week of screening visit is allowed. The last sample will be conclusive.)
Impaired kidney function with serum creatinine above or equal to 133 µmol/L (1.5 mg/dL) for males and above or equal to 124 µmol/L (1.4 mg/dL) for females. (One re-test within one week of screening visit is allowed. The last sample will be conclusive.)
Cardiac problems or uncontrolled treated/untreated severe hypertension (defined as systolic blood pressure above or equal to 180 mmHg and/or diastolic blood pressure above or equal to 100 mmHg)
Previous use of pre-mixed insulin products (pre-mixed insulin analogues or pre-mixed human preparations)
Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemic episode, during the last 12 months) or hypoglycaemic unawareness as judged by the Investigator or hospitalisation for diabetic ketoacidosis during the previous 6 months
Known proliferative retinopathy or maculopathy requiring treatment

Name	Affiliation	Role
Global Clinical Registry (GCR, 1452)	Novo Nordisk A/S	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Novo Nordisk Investigational Site		Alexandria		21131	Egypt
Novo Nordisk Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
28523482	Result	Chraibi A, Al-Herz S, Nguyen BD, Soeatmadji DW, Shinde A, Lakshmivenkataraman B, Assaad-Khalil SH. An RCT Investigating Patient-Driven Versus Physician-Driven Titration of BIAsp 30 in Patients with Type 2 Diabetes Uncontrolled Using NPH Insulin. Diabetes Ther. 2017 Aug;8(4):767-780. doi: 10.1007/s13300-017-0268-1. Epub 2017 May 18.

Label	URL
Clinical Trials at Novo Nordisk	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Subject-driven Titration	The subjects received BIAsp 30. The treatment dose was individually adjusted by the subjects themselves according to the titration algorithm every second week. Trial product was administered subcutaneously (s.c., under the skin) twice daily.
FG001	Investigator-driven Titration

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Subject-driven Titration	The subjects received BIAsp 30. The treatment dose was individually adjusted by the subjects themselves according to the titration algorithm every second week. Trial product was administered subcutaneously (s.c., under the skin) twice daily.
BG001	Investigator-driven Titration	The subjects received BIAsp 30. The treatment dose was adjusted according to the directions given by the investigator. Trial product was administered subcutaneously (s.c., under the skin) twice daily.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00076 BG00179 BG002155

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00054.4± 10.22 BG00154.9± 9.77 BG00254.7± 9.96

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00060 BG00156 BG002

HbA1c (%)

Mean

Standard Deviation

percentage of glycosylated haemoglobin

Title

Denominators

Categories

Title	Measurements
	BG0008.5± 0.88 BG0018.7± 0.78 BG002

Fasting plasma glucose (mg/dL)

Mean

Standard Deviation

mg/dL

Title

Denominators

Categories

Title	Measurements
	BG000156.8± 59.03 BG001148.5± 54.24 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change in HbA1c From Baseline

Change in HbA1c (%) from baseline to the end of the treatment period.

Full analysis set (FAS) included all randomised subjects.

Posted

Least Squares Mean

Standard Error

percentage change in HbA1c

Week 0, week 20

ID	Title	Description
OG000	Subject-driven Titration	The subjects received BIAsp 30. The treatment dose was individually adjusted by the subjects themselves according to the titration algorithm every second week. Trial product was administered subcutaneously (s.c., under the skin) twice daily.
OG001	Investigator-driven Titration	The subjects received BIAsp 30. The treatment dose was adjusted according to the directions given by the investigator. Trial product was administered subcutaneously (s.c., under the skin) twice daily.

Units	Counts
Participants	OG00076 OG00179

Title

Denominators

Categories

Title	Measurements
	OG000-1.27± 0.11 OG001-1.04± 0.11

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	The null-hypothesis was tested against the alternative hypothesis of non-inferiority as given by: H0: D > 0.4% against HA: D ≤ 0.4% where D is the mean treatment difference for change in HbA1c (subject-driven titration minus investigator-driven titration).	Regression, Linear	Analyses were adjusted for treatment, strata, country and baseline HbA1c	<0.001		Treatment difference	-0.23			2-Sided	95	-0.54	0.08					Non-Inferiority or Equivalence	Non-inferiority was to be considered confirmed if the upper bound of the two-sided 95% CI was below or equal to 0.4% or equivalently when the p-value for the one-sided test of H0: D > 0.4% against HA: D ≤ 0.4%, was less than or equal to 2.5%, where D is the mean treatment difference (subject-driven titration minus investigator-driven titration).

Secondary

Change in Fasting Plasma Glucose (FPG) (Laboratory Values) From Baseline

Change in FPG (laboratory values) from baseline to the end of the treatment period

Full analysis set (FAS) included all randomised subjects. Missing data were imputed using last observation carried forward (LOCF). A total of 150 subjects contributed to the analysis.

Posted

Mean

Standard Deviation

mg/dL

Week 0, week 20

ID	Title	Description
OG000	Subject-driven Titration	The subjects received BIAsp 30. The treatment dose was individually adjusted by the subjects themselves according to the titration algorithm every second week. Trial product was administered subcutaneously (s.c., under the skin) twice daily.
OG001	Investigator-driven Titration	The subjects received BIAsp 30. The treatment dose was adjusted according to the directions given by the investigator. Trial product was administered subcutaneously (s.c., under the skin) twice daily.

Units	Counts
Participants

Secondary

Number of Hypoglycaemic Episodes During the Trial From Baseline

The number of hypoglycaemic episodes (a blood glucose level of approximately 2.8 mmol/L [50 mg/dL] or plasma glucose level 3.1 mmol/L [56 mg/dL]) during the trial.

Full analysis set (FAS) included all randomised subjects. Missing data were imputed using last observation carried forward (LOCF). 154 subjects contributed to the analysis.

Posted

Number

episodes

Week 20

ID	Title	Description
OG000	Subject-driven Titration	The subjects received BIAsp 30. The treatment dose was individually adjusted by the subjects themselves according to the titration algorithm every second week. Trial product was administered subcutaneously (s.c., under the skin) twice daily.
OG001	Investigator-driven Titration	The subjects received BIAsp 30. The treatment dose was adjusted according to the directions given by the investigator. Trial product was administered subcutaneously (s.c., under the skin) twice daily.

Units	Counts
Participants

Secondary

Change in Patient Reported Outcomes: Treatment-Related Impact Measures for Diabetes (TRIM-D)

Mean change from baseline in Treatment Related Impact Measure - Diabetes (TRIM-D) scores. The score measured treatment satisfaction which included an overall score as well the subscale scores (daily life, diabetes management, compliance and psychological health). The scores were transformed to a 0-100 scale with higher scores indicating a better health state.

Full analysis set (FAS) included all randomised subjects.

Posted

Mean

Standard Deviation

scores on a scale

Week 0, week 20

ID	Title	Description
OG000	Subject-driven Titration	The subjects received BIAsp 30. The treatment dose was individually adjusted by the subjects themselves according to the titration algorithm every second week. Trial product was administered subcutaneously (s.c., under the skin) twice daily.
OG001	Investigator-driven Titration	The subjects received BIAsp 30. The treatment dose was adjusted according to the directions given by the investigator. Trial product was administered subcutaneously (s.c., under the skin) twice daily.

Units	Counts

Secondary

Change in Patient Reported Outcomes: Treatment-Related Impact Measures for Diabetes (TRIM-D)-Treatment Burden

Mean change from baseline in Treatment Related Impact Measure - Diabetes (TRIM-D) scores. The score measured treatment satisfaction which included a subscale score -treatment burden. The scores were transformed to a 0-100 scale with higher scores indicating a better health state.

Full analysis set (FAS) included all randomised subjects.

Posted

Mean

Standard Deviation

scores on a scale

Week 0, week 20

ID	Title	Description
OG000	Subject-driven Titration	The subjects received BIAsp 30. The treatment dose was individually adjusted by the subjects themselves according to the titration algorithm every second week. Trial product was administered subcutaneously (s.c., under the skin) twice daily.
OG001	Investigator-driven Titration	The subjects received BIAsp 30. The treatment dose was adjusted according to the directions given by the investigator. Trial product was administered subcutaneously (s.c., under the skin) twice daily.

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Subject-driven Titration	The subjects received BIAsp 30. The treatment dose was individually adjusted by the subjects themselves according to the titration algorithm every second week. Trial product was administered subcutaneously (s.c., under the skin) twice daily.			0	76	19	76
EG001	Investigator-driven Titration	The subjects received BIAsp 30. The treatment dose was adjusted according to the directions given by the investigator. Trial product was administered subcutaneously (s.c., under the skin) twice daily.			5	78	23	78

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Dyspepsia	Gastrointestinal disorders	MedDRA version 18.0	Systematic Assessment	EG0000 events0 affected76 at risk EG0011 events1 affected78 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA version 18.0	Systematic Assessment	EG0000 events0 affected76 at risk EG0011 events1 affected78 at risk
Localised infection	Infections and infestations	MedDRA version 18.0	Systematic Assessment	EG0000 events0 affected76 at risk EG0011 events1 affected78 at risk
Invasive ductal breast carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA version 18.0	Systematic Assessment	EG0000 events0 affected76 at risk EG0011 events1 affected78 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA version 18.0	Systematic Assessment	EG0000 events0 affected76 at risk EG0011 events1 affected78 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA version 18.0	Systematic Assessment	EG0004 events4 affected76 at risk EG0015 events5 affected78 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA version 18.0	Systematic Assessment	EG0004 events4 affected76 at risk EG0012 events2 affected78 at risk
Nasopharyngitis	Infections and infestations	MedDRA version 18.0	Systematic Assessment	EG0006 events6 affected76 at risk EG0017 events5 affected78 at risk
Influenza	Infections and infestations	MedDRA version 18.0	Systematic Assessment	EG0006 events6 affected76 at risk EG0014 events4 affected78 at risk
Headache	Nervous system disorders	MedDRA version 18.0	Systematic Assessment	EG00010 events8 affected76 at risk EG0016 events6 affected78 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA version 18.0	Systematic Assessment	EG0003 events2 affected76 at risk EG0015 events5 affected78 at risk

ID	Term
D003920	Diabetes Mellitus
D003924	Diabetes Mellitus, Type 2

ID	Term
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases