Glargine Versus NPH in Patients With Chronic Kidney Disease | NCT02451917

Glargine Versus NPH in Patients With Chronic Kidney Disease | NCT02451917 | Trialant

Description Module

Brief Summary

Chronic kidney disease (CKD) is one of the most common microvascular complications of diabetes mellitus, and it is the leading cause of end stage renal disease on developed countries. The CKD diagnosis and its progression require re-evaluation of hypoglycemic therapy and constant dosing adjustments, in order to optimize glycemic control and minimize its side effects. Long acting insulin analogs and its pharmacokinetics have not been studied through different stages of kidney disease and there is no consensus defining the appropriate dosing adjustment based on the glomerular filtration rate (GFR). This research project will compare the glycemic response to intensive insulin treatment with NPH insulin and basal insulin analog (insulin glargine) in type 2 diabetes (DM 2) patients with CKD stages 3 and 4. Patients and methods - Inclusion Criteria: DM 2 patients with CKD secondary to diabetic nephropathy and GFR of 15-59 ml/min/1.73m². Exclusion Criteria: Patients with systemic neoplasia, HIV, CKD or nephropathy from other etiologies, severe psychiatric disorders and pregnant women. Study design: This study consists of a randomized, cross-over, open-label controlled clinical trial. Patients will be randomly divided into two groups: GROUP 1 - insulin analog glargine once a day and GROUP 2 - NPH human insulin, three applications per day, both group will be treated with insulin lispro at mealtime. The laboratory tests will be performed at baseline and 12, 24, 36 and 48 weeks after the study start. During routine medical appointments will be analyzed self- monitoring of capillary blood glucose (SMBG) and the hypoglycemia score. After 24 weeks the basal insulin will be changed, i.e. patients using NPH insulin will receive insulin glargine and patients on insulin glargine will be changed to NPH insulin. A CGMS will be carried out at 24 and 48 weeks. Methodology: The metabolic profile will be evaluated throughout SMBG; biochemical, hormonal and hematological measurements; hypoglycemia score and CGMS. Statistical analysis will be performed using comparative descriptive analyzes, such as chi-square distribution, t-test and non-parametric tests. Analyze of data CGMS will include the area under the curve and the related statistic. Finally, logistic regression models will be adopted to evaluate the effect of the treatment on the several variables in question.

Detailed Description

This study consists of a randomized, cross-over, open-label controlled clinical trial. Randomized patients will be allocated alternately into two groups to receive the following therapies: GROUP 1 - insulin analog glargine once a day associated to insulin lispro at mealtime and GROUP 2 - NPH human insulin, three applications per day ( breakfast, lunch and bedtime) and insulin lispro at mealtime. Patients receiving insulin NPH plus insulin lispro will be oriented to mix both of them in the same syringe at breakfast and lunchtime. The laboratory tests will be performed at baseline and 12, 24, 36 and 48 weeks after the study start. During routine medical appointments the patient should bring the self- monitoring of capillary blood glucose (SMBG), eight points per day once a week, and hypoglycemia score.

After 24 weeks of insulin therapy, a continuous glucose monitoring system (CGMS) will be implemented for three days, and after that, the basal insulin changed i.e. patients using NPH insulin will receive insulin glargine and patients on insulin glargine will be changed to NPH insulin, both groups will keep insulin lispro before meals. A new CGMS will be carried out 24 weeks after therapy has been changed. Methodology: The metabolic profile will be evaluated throughout SMBG; biochemical, hormonal and hematological measurements; hypoglycemia score and CGMS (Medtronic/Northridge, CA). All randomized patients who use at least one dose of any study treatment will be considered in the Intent-to-treat (ITT) population. The initial plan is to randomize 40 patients, assuming a drop-out rate of 15%, to obtain a sample size of at least 34 randomized patients. .Statistical analysis will be performed using comparative descriptive analyzes, such as chi-square distribution, t-test and non-parametric tests. Analyze of data CGMS will include the area under the curve and the related statistic. Finally, logistic regression models will be adopted to evaluate the effect of the treatment on the several variables in question.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Glargine insulin	Experimental	This is an open-label, randomized, two-way crossover study , one is IGlar/INPH treatment sequence and, another is INPH/IGlar sequence. Wherein, IGlar refers to glargine insulin and INPH refers to NPH insulin. At the end of the study, all data acquired during the use of insulin glargine, regardless of the sequence were grouped as glargine.	Drug: Glargine insulin
NPH insulin	Active Comparator	This is an open-label, randomized, two-way crossover study , one is IGlar/INPH treatment sequence and, another is INPH/IGlar sequence. Wherein, IGlar refers to glargine insulin and INPH refers to NPH insulin. At the end of the study, all data acquired during the use of NPH insulin, regardless of the sequence were grouped as NPH.	Drug: NPH insulin

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Glargine insulin	Drug	The initial insulin dose for those randomized to IGlar was 80% of the total daily NPH dose that was being discontinued. All of them had pre-prandial Regular insulin switched to Lispro insulin (Humalog™, Lilly, Brazil), at the same dose as in use previously. After 24 weeks, basal insulins were switched; in other words, individuals on IGlar in the first period switched to INPH, and the doses of pre-meal insulin were sustained

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Difference in A1c Levels	A1c using high performance liquid chromatography measured in percentage	baseline and 24 weeks
Number of Hypoglycemic Events	Hypoglycemia was defined by capillary glycemia< 70 mg/dL (3.9 mmol/L), even if it was not accompanied by typical symptoms. Otherwise, hypoglycemia was classified as "severe" with SMBG below 50 mg/dL (2.8 mmol/L) or when it resulted in stupor, seizure, or unconsciousness that precluded self-treatment, thus requiring the assistance of another individual. Nocturnal events were defined as SMBG < 70mg/dL occurring after midnight and before wake-up in the morning (before 7:00am)12.	between 1rst and 24 weeks of each treatment arm

Other Outcomes

Measure	Description	Time Frame
Glycemic Variability	In order to observe variability in interstitial glucose levels related to the therapy in use, participants wore a blinded CGM for 3 days. Changes in glycemic patterns were expressed by the average daily time spent in hypoglycemia (≤70 mg/dL or <3.9 mmol/L), hyperglycemia (>180 mg/dL or >10 mmol/L) and euglycemia (70-180 mg/dL or 3.9-10 mmol/L).	24 week

Contacts/Locations Module

Overall Officials

Name	Affiliation	Role
Marcia S Queiroz, MD, PhD	Assistant Professor at Division of Endocrinology and Metabolism, Department of Internal Medicine, Clinic Hospital of the University of São Paulo Medical School	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
University of Sao Paulo		São Paulo		05410001	Brazil

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
33166419	Derived	Semlitsch T, Engler J, Siebenhofer A, Jeitler K, Berghold A, Horvath K. (Ultra-)long-acting insulin analogues versus NPH insulin (human isophane insulin) for adults with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2020 Nov 9;11(11):CD005613. doi: 10.1002/14651858.CD005613.pub4.
31383366	Derived

Arm/Group Information

ID	Title	Description
FG000	Glargine Insulin, Then NPH Insulin	The initial insulin dose for those randomized to IGlar was 80% of the total daily NPH dose that was being discontinued. All of them had pre-prandial Regular insulin switched to Lispro insulin (Humalog™, Lilly, Brazil), at the same dose as in use previously. After 24 weeks, basal insulins were switched; in other words, individuals on IGlar in the first period switched to INPH, and the doses of pre-meal insulin were sustained
FG001	NPH Insulin, Then Glargine Insulin	The same total daily NPH insulin dose was maintained for those randomized to INPH. All of them had pre-prandial Regular insulin (Humulin R™, Lilly, Brazil) switched to Lispro insulin (Humalog™, Lilly, Brazil), at the same dose as in use previously. . After 24 weeks, basal insulins were switched; in other words, individuals on NPH in the first period switched to glargine insulin, and the doses of pre-meal insulin were sustained.

Periods

Title

Milestones

Reasons Not Completed

First Intervention (24 Weeks)

Type	Comment	Milestone Data
STARTED		FG00016 subjects FG00118 subjects
COMPLETED		FG00014 subjects FG00115 subjects
NOT COMPLETED		FG0002 subjects FG0013 subjects

Type	Comment	Reasons
Lost to Follow-up		FG0002 subjects FG0010 subjects
Death		FG0000 subjects FG001

Second Intervention (24 Weeks)

Type	Comment	Milestone Data
STARTED		FG00014 subjects FG00115 subjects
COMPLETED		FG00014 subjects FG001

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Glargine Insulin, Then NPH Insulin	The initial insulin dose for those randomized to IGlar was 80% of the total daily NPH dose that was being discontinued. All of them had pre-prandial Regular insulin switched to Lispro insulin (Humalog™, Lilly, Brazil), at the same dose as in use previously. After 24 weeks, basal insulins were switched; in other words, individuals on IGlar in the first period switched to INPH, and the doses of pre-meal insulin were sustained

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

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

Difference in A1c Levels

A1c using high performance liquid chromatography measured in percentage

Primary endpoint A1c was assessed using an analysis of covariance (ANOVA) model.

Posted

Mean

Standard Deviation

percentage

baseline and 24 weeks

ID	Title	Description
OG000	Glargine Insulin Period	This is an open-label, randomized, two-way crossover study, one is IGlar/INPH treatment sequence and, another is INPH/IGlar sequence. Wherein, IGlar refers to glargine insulin and INPH refers to NPH insulin. At the end of the study, all data acquired during the use of insulin glargine, regardless of the sequence were grouped as glargine insulin.
OG001	NPH Insulin Period

Adverse Events Module

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	Glargine Insulin	This is an open-label, randomized, two-way crossover study , one is IGlar/INPH treatment sequence and, another is INPH/IGlar sequence. Wherein, IGlar refers to glargine insulin and INPH refers to NPH insulin. At the end of the study, all data acquired during the use of insulin glargine, regardless of the sequence were grouped as glargine. Glargine insulin: The initial insulin dose for those randomized to IGlar was 80% of the total daily NPH dose that was being discontinued. All of them had pre-prandial Regular insulin switched to Lispro insulin (Humalog™, Lilly, Brazil), at the same dose as in use previously. After 24 weeks, basal insulins were switched; in other words, individuals on IGlar in the first period switched to INPH, and the doses of pre-meal insulin were sustained

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Severe hypoglycemia	Nervous system disorders		Systematic Assessment	stupor, seizure, or unconsciousness that precluded self-treatment, thus requiring the assistance of another individual

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Marcia Silva Queiroz, MD, PhD	Endocrinology Division, University of São Paulo Medical School,	+ 5511 26616293		marcia.queiroz@hc.fm.usp.br

Condition Browse Module

ID	Term
D003924	Diabetes Mellitus, Type 2
D051436	Renal Insufficiency, Chronic

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases

Intervention Browse Module

ID	Term
D000069036	Insulin Glargine
D007336	Insulin, Isophane
D000068880	Isophane Insulin, Human

ID	Term
D049528	Insulin, Long-Acting
D061385	Insulins
D010187	Pancreatic Hormones
D036361	Peptide Hormones

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	A sample size of 34 participants (16 randomized to sequence IGlar/INPH and 18 randomized to sequence INPH/IGlar) provided 90% power to detect a mean difference of 0.7% in the primary endpoint (A1c), considering a 15% dropout rate and assuming an SD of 0.85%, and a type I error of 5%. Test for data normality (Kolmogorov-Smirnov statistics) was performed at baseline for each sequence of the therapy.	ANOVA		0.00045	The intention-to-treat population consisted of all randomized participants.													Non-Inferiority or Equivalence	A sample size of 34 participants (16randomized to sequence IGlar/INPH and 18randomized to sequence INPH/IGlar) provided 90% power to detect a mean difference of 0.7% in the primary endpoint(A1c), considering a 15% dropout rate and assuming an SD of 0.85%, and a type I error of 5%.

Primary

Number of Hypoglycemic Events

Hypoglycemia was defined by capillary glycemia< 70 mg/dL (3.9 mmol/L), even if it was not accompanied by typical symptoms. Otherwise, hypoglycemia was classified as "severe" with SMBG below 50 mg/dL (2.8 mmol/L) or when it resulted in stupor, seizure, or unconsciousness that precluded self-treatment, thus requiring the assistance of another individual. Nocturnal events were defined as SMBG < 70mg/dL occurring after midnight and before wake-up in the morning (before 7:00am)12.

Endpoint hypoglycemia was assessed using an analysis of covariance (ANOVA) model

Posted

Mean

Standard Deviation

events per patients during 24 weeks

between 1rst and 24 weeks of each treatment arm

ID	Title	Description
OG000	Glargine Insulin Period	This is an open-label, randomized, two-way crossover study, one is IGlar/INPH treatment sequence and, another is INPH/IGlar sequence. Wherein, IGlar refers to glargine insulin and INPH refers to NPH insulin. At the end of the study, all data acquired during the use of insulin glargine, regardless of the sequence were grouped as glargine insulin.
OG001	NPH Insulin Period	This is an open-label, randomized, two-way crossover study, one is IGlar/INPH treatment sequence and, another is INPH/IGlar sequence. Wherein, IGlar refers to glargine insulin and INPH refers to NPH insulin. At the end of the study, all data acquired during the use of NPH insulin, regardless of the sequence were grouped as NPH insulin.

Units	Counts
Participants	OG00034 OG00134

Title

Denominators

Categories

total hypoglycemic events

Title	Measurements
	OG0004.87± 5.39 OG0016.34± 9.37

nocturnal hypoglycemias

Title	Measurements
	OG000

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	Analysis of covariance (ANOVA) model - total hypoglycemic events per patient during 24 weeks	ANOVA		0.35	Analysis of covariance (ANOVA) model - total hypoglycemic events per patient during 24 weeks	number of total events per patient	0			2-Sided						The calculated value for the estimation parameter was zero, since the best treatment option for those with diabetes is reach a good glycemic control without hypoglycemia.		Non-Inferiority or Equivalence

Other Pre-specified

Glycemic Variability

In order to observe variability in interstitial glucose levels related to the therapy in use, participants wore a blinded CGM for 3 days. Changes in glycemic patterns were expressed by the average daily time spent in hypoglycemia (≤70 mg/dL or <3.9 mmol/L), hyperglycemia (>180 mg/dL or >10 mmol/L) and euglycemia (70-180 mg/dL or 3.9-10 mmol/L).

Patients were excluded from the analysis because of unfamiliarity with mechanical procedures related to the CGM use, visual impairment or technical problems with the sensor measurement.

Posted

Mean

Standard Deviation

percentage of time

24 week

ID	Title	Description
OG000	Glargine Insulin Period	This is an open-label, randomized, two-way crossover study, one is IGlar/INPH treatment sequence and, another is INPH/IGlar sequence. Wherein, IGlar refers to glargine insulin and INPH refers to NPH insulin. At the end of the study, all data acquired during the use of NPH insulin, regardless of the sequence were grouped as glargine insulin.
OG001	NPH Insulin Period	This is an open-label, randomized, two-way crossover study, one is IGlar/INPH treatment sequence and, another is INPH/IGlar sequence. Wherein, IGlar refers to glargine insulin and INPH refers to NPH insulin. At the end of the study, all data acquired during the use of NPH insulin, regardless of the sequence were grouped as NPH insulin.

Units	Counts
Participants	OG00024 OG00124

Title

Denominators

Categories

hyperglycemia

Title	Measurements
	OG00030± 19 OG00138± 19

normoglycemia

Title	Measurements
	OG000

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	A sample size of 34 participants (16 randomized to sequence IGlar/INPH and 18 randomized to sequence INPH/IGlar) provided 90% power and assuming an SD of 0.85%, and a type I error of 5%.	t-test, 1 sided		<0.05														Non-Inferiority or Equivalence	t-test was applied to compare percentages of the time spent in hypoglycemia, hyperglycemia and euglycemia on CGM readings.

Other Pre-specified

Total Daily Insulin Dose

Daily total insulin dose at baseline compared to dose at week 24.

Randomization was stratified by the A1c value at baseline: <9.0% or ≥9.0%, in a 1:1 ratio, and the individuals who met all inclusion-criteria were allocated alternately to either an IGlar/INPH or an INPH/IGlar treatment sequence.

Posted

Mean

Standard Deviation

units/Kg/day

baseline and 24 weeks

ID	Title	Description
OG000	Glargine Insulin	This is an open-label, randomized, two-way crossover study, one is IGlar/INPH treatment sequence and, another is INPH/IGlar sequence. Wherein, IGlar refers to glargine insulin and INPH refers to NPH insulin. At the end of the study, all data acquired during the use of insulin glargine, regardless of the sequence were grouped as glargine insulin.
OG001	NPH Insulin	This is an open-label, randomized, two-way crossover study, one is IGlar/INPH treatment sequence and, another is INPH/IGlar sequence. Wherein, IGlar refers to glargine insulin and INPH refers to NPH insulin. At the end of the study, all data acquired during the use of NPH insulin, regardless of the sequence were grouped as NPH insulin.

Units	Counts
Participants	OG00034 OG00134

Title

Denominators

Categories

Baseline

Title	Measurements
	OG0000.61± 0.21 OG0010.63± 0.21

24 weeks treatment

Title	Measurements
	OG000

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	A sample size of 34 participants (16randomized to sequence IGlar/INPH and 18 randomized to sequence INPH/IGlar) provided 90% power and assuming an SD of 0.85%, and a type I error of 5%.	ANOVA		0.668														Non-Inferiority or Equivalence	A sample size of 34 participants (16randomized to sequence IGlar/INPH and 18 randomized to sequence INPH/IGlar) provided 90% power and assuming an SD of 0.85%, and a type I error of 5%.

Other Pre-specified

Body Mass Index (BMI)

The BMI is defined as the body mass divided by the square of the body height, and is universally expressed in units of kg/m2, resulting from mass in kilograms and height in metres.

BMI endpoint was assessed using an analysis of covariance (ANOVA) model.

Posted

Mean

Standard Deviation

Kg/m²

baseline and 24 weeks

ID	Title	Description
OG000	Glargine Insulin Period	This is an open-label, randomized, two-way crossover study, one is IGlar/INPH treatment sequence and, another is INPH/IGlar sequence. Wherein, IGlar refers to glargine insulin and INPH refers to NPH insulin. At the end of the study, all data acquired during the use of insulin glargine, regardless of the sequence were grouped as glargine insulin.
OG001	NPH Insulin Period	This is an open-label, randomized, two-way crossover study, one is IGlar/INPH treatment sequence and, another is INPH/IGlar sequence. Wherein, IGlar refers to glargine insulin and INPH refers to NPH insulin. At the end of the study, all data acquired during the use of NPH insulin, regardless of the sequence were grouped as NPH insulin.

Units	Counts
Participants	OG00034 OG00134

Title

Denominators

Categories

Baseline

Title	Measurements
	OG00029.7± 4.7 OG00130.0± 4.3

24 weeks treatement

Title	Measurements
	OG000

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	A sample size of 34 participants (16 randomized to sequence IGlar/INPH and 18r andomized to sequence INPH/IGlar) provided 90% power and assuming an SD of 0.85%, and a type I error of 5%.	ANOVA		0.999														Non-Inferiority or Equivalence	A sample size of 34 participants (16 randomized to sequence IGlar/INPH and 18r andomized to sequence INPH/IGlar) provided 90% power and assuming an SD of 0.85%, and a type I error of 5%.

Other Pre-specified

Serum Creatinine

Creatinine is measured in milligrams per deciliter of blood (mg/dL

Creatinine endpoint was assessed using an analysis of covariance (ANOVA) model.

Posted

Mean

Standard Deviation

mg/dL

baseline and 24 weeks

ID	Title	Description
OG000	Glargine Insulin Period	This is an open-label, randomized, two-way crossover study, one is IGlar/INPH treatment sequence and, another is INPH/IGlar sequence. Wherein, IGlar refers to glargine insulin and INPH refers to NPH insulin. At the end of the study, all data acquired during the use of insulin glargine, regardless of the sequence were grouped as glargine insulin.
OG001	NPH Insulin Period	This is an open-label, randomized, two-way crossover study, one is IGlar/INPH treatment sequence and, another is INPH/IGlar sequence. Wherein, IGlar refers to glargine insulin and INPH refers to NPH insulin. At the end of the study, all data acquired during the use of NPH insulin, regardless of the sequence were grouped as NPH insulin.

Units	Counts
Participants	OG00034 OG00134

Title

Denominators

Categories

Baseline

Title	Measurements
	OG0002.4± 0.7 OG0012.5± 1.0

24 weeks treatement

Title	Measurements
	OG000

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	A sample size of 34 participants (16randomized to sequence IGlar/INPH and 18 randomized to sequence INPH/IGlar) provided 90% power and assuming an SD of 0.85%, and a type I error of 5%.	ANOVA		0.999														Non-Inferiority or Equivalence	A sample size of 34 participants (16randomized to sequence IGlar/INPH and 18 randomized to sequence INPH/IGlar) provided 90% power and assuming an SD of 0.85%, and a type I error of 5%.

Other Pre-specified

Estimated Glomerular Filtration Rate (eGFR) Calculated by CKD-EPI

Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation is one of the most widely used IDMS traceable equations for estimating GFR in patients age 18 and over. CKD-EPI equation includes variables for age, gender, and race, which may allow providers to observe that CKD is present despite a serum creatinine concentration that appears to fall within or just above the normal reference interval.

CKD-EPI equation expressed as a single equation: GFR = 141 × min (Scr /κ, 1)α × max(Scr /κ, 1)-1.209 × 0.993Age × 1.018 [if female] × 1.159 [if black] where: Scr is serum creatinine in mg/dL, κ is 0.7 for females and 0.9 for males, α is -0.329 for females and -0.411 for males,min indicates the minimum of Scr /κ or 1, and max indicates the maximum of Scr /κ or 1.

Posted

Mean

Standard Deviation

ml/min/1.7m²

baseline and 24 weeks

ID	Title	Description
OG000	Glargine Insulin Period	This is an open-label, randomized, two-way crossover study, one is IGlar/INPH treatment sequence and, another is INPH/IGlar sequence. Wherein, IGlar refers to glargine insulin and INPH refers to NPH insulin. At the end of the study, all data acquired during the use of insulin glargine, regardless of the sequence were grouped as glargine insulin.
OG001	NPH Insulin Period	This is an open-label, randomized, two-way crossover study, one is IGlar/INPH treatment sequence and, another is INPH/IGlar sequence. Wherein, IGlar refers to glargine insulin and INPH refers to NPH insulin. At the end of the study, all data acquired during the use of NPH insulin, regardless of the sequence were grouped as NPH insulin.

Units	Counts
Participants	OG00034 OG00134

Title

Denominators

Categories

Baseline

Title	Measurements
	OG00028.0± 9.6 OG00127.4± 9.1

24 weeks treatement

Title	Measurements
	OG000

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	A sample size of 34 participants (16randomized to sequence IGlar/INPH and 18 randomized to sequence INPH/IGlar) provided 90% power and assuming an SD of 0.85%, and a type I error of 5%.	ANOVA		0.994														Non-Inferiority or Equivalence	A sample size of 34 participants (16randomized to sequence IGlar/INPH and 18 randomized to sequence INPH/IGlar) provided 90% power and assuming an SD of 0.85%, and a type I error of 5%.