药物信息为Lantus (Physicians Total Care, Inc.): 14 CLINICAL STUDIES
- 1. INDICATIONS AND USAGE
- 2. DOSAGE AND ADMINISTRATION
- 3. DOSAGE FORMS AND STRENGTHS
- 4. CONTRAINDICATIONS
- 5. WARNINGS AND PRECAUTIONS
- 6. ADVERSE REACTIONS
- 7 DRUG INTERACTIONS
- 8 USE IN SPECIFIC POPULATIONS
- 10 OVERDOSAGE
- 11 DESCRIPTION
- 12 CLINICAL PHARMACOLOGY
- 13 NONCLINICAL TOXICOLOGY
- 14 CLINICAL STUDIES
- 16 HOW SUPPLIED/STORAGE AND HANDLING
- 17 PATIENT COUNSELING INFORMATION
- PRINCIPAL DISPLAY PANEL
- 外部链接相关的Lantus (Physicians Total Care, Inc.)
The safety and effectiveness of LANTUS given once-daily at bedtime was compared to that of once-daily and twice-daily NPH insulin in open-label, randomized, active-controlled, parallel studies of 2,327 adult patients and 349 pediatric patients with type 1 diabetes mellitus and 1,563 adult patients with type 2 diabetes mellitus (see Tables 8–11). In general, the reduction in glycated hemoglobin (HbA1c) with LANTUS was similar to that with NPH insulin. The overall rates of hypoglycemia did not differ between patients with diabetes treated with LANTUS compared to NPH insulin [See Adverse Reactions (6.1)].
Type 1 Diabetes–Adult (see Table 8).
In two clinical studies (Studies A and B), patients with type 1 diabetes (Study A; n=585, Study B; n=534) were randomized to 28 weeks of basal-bolus treatment with LANTUS or NPH insulin. Regular human insulin was administered before each meal. LANTUS was administered at bedtime. NPH insulin was administered once daily at bedtime or in the morning and at bedtime when used twice daily.
In another clinical study (Study C), patients with type 1 diabetes (n=619) were randomized to 16 weeks of basal-bolus treatment with LANTUS or NPH insulin. Insulin lispro was used before each meal. LANTUS was administered once daily at bedtime and NPH insulin was administered once or twice daily.
In these 3 studies, LANTUS and NPH insulin had similar effects on HbA1c (Table 8) with a similar overall rate of hypoglycemia [See Adverse Reactions (6.1)].
Table 8: Type 1 Diabetes Mellitus–Adult Study A Study B Study C Treatment duration 28 weeks 28 weeks 16 weeks Treatment in combination with Regular insulin Regular insulin Insulin lispro LANTUS NPH LANTUS NPH LANTUS NPH Number of subjects treated 292 293 264 270 310 309 HbA1c Baseline HbA1c 8.0 8.0 7.7 7.7 7.6 7.7 Adj. mean change from baseline +0.2 +0.1 -0.2 -0.2 -0.1 -0.1 LANTUS - NPH +0.1 +0.1 0.0 95% CI for Treatment difference (0.0; +0.2) (-0.1; +0.2) (-0.1; +0.1) Basal insulin dose Baseline mean 21 23 29 29 28 28 Mean change from baseline -2 0 -4 +2 -5 +1 Total insulin dose Baseline mean 48 52 50 51 50 50 Mean change from baseline -1 0 0 +4 -3 0 Fasting blood glucose (mg/dL) Baseline mean 167 166 166 175 175 173 Adj. mean change from baseline -21 -16 -20 -17 -29 -12 Body weight (kg) Baseline mean 73.2 74.8 75.5 75.0 74.8 75.6 Mean change from baseline 0.1 -0.0 0.7 1.0 0.1 0.5
Type 1 Diabetes–Pediatric (see Table 9).
In a randomized, controlled clinical study (Study D), pediatric patients (age range 6 to 15 years) with type 1 diabetes (n=349) were treated for 28 weeks with a basal-bolus insulin regimen where regular human insulin was used before each meal. LANTUS was administered once daily at bedtime and NPH insulin was administered once or twice daily. Similar effects on HbA1c (Table 9) and the incidence of hypoglycemia were observed in both treatment groups [See Adverse Reactions (6.1)].
Table 9: Type 1 Diabetes Mellitus–Pediatric Study D Treatment duration 28 weeks Treatment in combination with Regular insulin LANTUS NPH Number of subjects treated 174 175 HbA1c Baseline mean 8.5 8.8 Adj. mean change from baseline +0.3 +0.3 LANTUS - NPH 0.0 95% CI for Treatment difference (-0.2; +0.3) Basal insulin dose Baseline mean 19 19 Mean change from baseline -1 +2 Total insulin dose Baseline mean 43 43 Mean change from baseline +2 +3 Fasting blood glucose (mg/dL) Baseline mean 194 191 Adj. mean change from baseline -23 -12 Body weight (kg) Baseline mean 45.5 44.6 Mean change from baseline 2.2 2.5
Type 2 Diabetes–Adult (see Table 10).
In a randomized, controlled clinical study (Study E) (n=570), LANTUS was evaluated for 52 weeks in combination with oral anti-diabetic medications (a sulfonylurea, metformin, acarbose, or combinations of these drugs). LANTUS administered once daily at bedtime was as effective as NPH insulin administered once daily at bedtime in reducing HbA1c and fasting glucose (Table 10). The rate of hypoglycemia was similar in LANTUS and NPH insulin treated patients [See Adverse Reactions (6.1)].
In a randomized, controlled clinical study (Study F), in patients with type 2 diabetes not using oral anti-diabetic medications (n=518), a basal-bolus regimen of LANTUS once daily at bedtime or NPH insulin administered once or twice daily was evaluated for 28 weeks. Regular human insulin was used before meals, as needed. LANTUS had similar effectiveness as either once- or twice-daily NPH insulin in reducing HbA1c and fasting glucose (Table 10) with a similar incidence of hypoglycemia [See Adverse Reactions (6.1)].
In a randomized, controlled clinical study (Study G), patients with type 2 diabetes were randomized to 5 years of treatment with once-daily LANTUS or twice-daily NPH insulin. For patients not previously treated with insulin, the starting dose of LANTUS or NPH insulin was 10 units daily. Patients who were already treated with NPH insulin either continued on the same total daily NPH insulin dose or started LANTUS at a dose that was 80% of the total previous NPH insulin dose. The primary endpoint for this study was a comparison of the progression of diabetic retinopathy by 3 or more steps on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. HbA1c change from baseline was a secondary endpoint. Similar glycemic control in the 2 treatment groups was desired in order to not confound the interpretation of the retinal data. Patients or study personnel used an algorithm to adjust the LANTUS and NPH insulin doses to a target fasting plasma glucose =100 mg/dL. After the LANTUS or NPH insulin dose was adjusted, other anti-diabetic agents, including pre-meal insulin were to be adjusted or added. The LANTUS group had a smaller mean reduction from baseline in HbA1c compared to the NPH insulin group, which may be explained by the lower daily basal insulin doses in the LANTUS group (Table 10). Both treatment groups had a similar incidence of reported symptomatic hypoglycemia. The incidences of severe symptomatic hypoglycemia are given in Table 6 [See Adverse Reactions (6.1)].
(*) In Study G, the baseline dose of basal or total insulin was the first available on-treatment dose prescribed during the study (on visit month 1.5).
Table 10: Type 2 Diabetes Mellitus–Adult Study E Study F Study G Treatment duration 52 weeks 28 weeks 5 years Treatment in combination with Oral agents Regular insulin Regular insulin LANTUS NPH LANTUS NPH LANTUS NPH Number of subjects treated 289 281 259 259 513 504 HbA1c Baseline mean 9.0 8.9 8.6 8.5 8.4 8.3 Adj. mean change from baseline -0.5 -0.4 -0.4 -0.6 -0.6 -0.8 LANTUS - NPH -0.1 +0.2 +0.2 95% CI for Treatment difference (-0.3; +0.1) (0.0; +0.4) (+0.1; +0.4) Basal insulin dose (*) Baseline mean 14 15 44.1 45.5 39 44 Mean change from baseline +12 +9 -1 +7 +23 +30 Total insulin dose (*) Baseline mean 14 15 64 67 48 53 Mean change from baseline +12 +9 +10 +13 +41 +40 Fasting blood glucose (mg/dL) Baseline mean 179 180 164 166 190 180 Adj. mean change from baseline -49 -46 -24 -22 -45 -44 Body weight (kg) Baseline mean 83.5 82.1 89.6 90.7 100 99 Adj. mean change from baseline 2.0 1.9 0.4 1.4 3.7 4.8
LANTUS Timing of Daily Dosing (see Table 11).
The safety and efficacy of LANTUS administered pre-breakfast, pre-dinner, or at bedtime were evaluated in a randomized, controlled clinical study in patients with type 1 diabetes (study H, n=378). Patients were also treated with insulin lispro at mealtime. LANTUS administered at different times of the day resulted in similar reductions in HbA1c compared to that with bedtime administration (see Table 11). In these patients, data are available from 8-point home glucose monitoring. The maximum mean blood glucose was observed just prior to injection of LANTUS regardless of time of administration.
In this study, 5% of patients in the LANTUS-breakfast arm discontinued treatment because of lack of efficacy. No patients in the other two arms discontinued for this reason. The safety and efficacy of LANTUS administered pre-breakfast or at bedtime were also evaluated in a randomized, active-controlled clinical study (Study I, n=697) in patients with type 2 diabetes not adequately controlled on oral anti-diabetic therapy. All patients in this study also received glimepiride 3 mg daily. LANTUS given before breakfast was at least as effective in lowering HbA1c as LANTUS given at bedtime or NPH insulin given at bedtime (see Table 11).
** total number of patients evaluable for safety(*) Intent to treat(**) Not applicable
Table 11: LANTUS Timing of Daily Dosing in Type 1 (Study H) and Type 2 (Study I) Diabetes Mellitus Study H Study I Treatment duration 24 weeks 24 weeks Treatment in combination with: Insulin lispro Glimepiride LANTUS LANTUS LANTUS LANTUS LANTUS NPH Breakfast Dinner Bedtime Breakfast Bedtime Bedtime Number of subjects treated (*) 112 124 128 234 226 227 HbA1c Baseline mean 7.6 7.5 7.6 9.1 9.1 9.1 Mean change from baseline -0.2 -0.1 0.0 -1.3 -1.0 -0.8 Basal insulin dose (U) Baseline mean 22 23 21 19 20 19 Mean change from baseline 5 2 2 11 18 18 Total insulin dose (U) NA (**) NA NA Baseline mean 52 52 49 Mean change from baseline 2 3 2 Body weight (kg) Baseline mean 77.1 77.8 74.5 80.7 82 81 Mean change from baseline 0.7 0.1 0.4 3.9 3.7 2.9
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