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Effect of a Fixed Pramlintide: Insulin Dose Ratio on Postprandial Glucose in Type 1 Diabetes Mellitus

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ClinicalTrials.gov Identifier: NCT02500979
Recruitment Status : Completed
First Posted : July 17, 2015
Results First Posted : November 2, 2018
Last Update Posted : November 2, 2018
Sponsor:
Collaborator:
Juvenile Diabetes Research Foundation
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Crossover Assignment;   Masking: Single (Participant);   Primary Purpose: Treatment
Condition Type 1 Diabetes Mellitus
Interventions Drug: Pramlintide acetate
Drug: Placebo
Drug: Lispro insulin U-100
Drug: Regular insulin U-100
Enrollment 34
Recruitment Details The first subject was enrolled in the study (at Visit 2) on 27 August 2015. A total of 79 subjects were screened and 34 subjects were randomized at 3 sites in the United States. One additional subject was randomized in error and was discontinued prior to receiving any study medication. The last subject completed the study on 05 August 2016.
Pre-assignment Details Eligible study subjects were males and females, aged ≥18 years and ≤70 years at the time of screening with a prior diagnosis of type 1 diabetes mellitus (T1DM) and an HbA1c value of ≥7.2% and ≤9.0% at screening.
Arm/Group Title Pramlintide First, Then Placebo Placebo First, Then Pramlintide
Hide Arm/Group Description (Treatment Sequence A) (Treatment Sequence B)
Period Title: Period 1
Started [1] 16 17
Completed [2] 12 16
Not Completed 4 1
Reason Not Completed
Hyperglycemia             1             0
Severe non-compliance to protocol             0             1
Adverse Event             1             0
Subject decision             2             0
[1]
(Randomized Analysis Set)
[2]
Number of subjects that entered Period 2
Period Title: Period 2
Started [1] 12 16
Completed [2] 11 16
Not Completed 1 0
Reason Not Completed
Change in risk             1             0
[1]
(Randomized Analysis Set)
[2]
Completed Period 2
Arm/Group Title Pramlintide First, Then Placebo Placebo First, Then Pramlintide Total
Hide Arm/Group Description (Treatment Sequence A) - Safety Analysis Set (Treatment Sequence B) - Safety Analysis Set Total of all reporting groups
Overall Number of Baseline Participants 16 16 32
Hide Baseline Analysis Population Description
Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Age, Categorical   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 16 participants 32 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
14
  87.5%
16
 100.0%
30
  93.8%
>=65 years
2
  12.5%
0
   0.0%
2
   6.3%
[1]
Measure Analysis Population Description: Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 16 participants 16 participants 32 participants
45.1  (14.83) 38.9  (12.68) 42.0  (13.92)
[1]
Measure Analysis Population Description: Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 16 participants 32 participants
Female
13
  81.3%
12
  75.0%
25
  78.1%
Male
3
  18.8%
4
  25.0%
7
  21.9%
[1]
Measure Analysis Population Description: Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Ethnicity (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 16 participants 32 participants
Hispanic or Latino
0
   0.0%
2
  12.5%
2
   6.3%
Not Hispanic or Latino
16
 100.0%
14
  87.5%
30
  93.8%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Analysis Population Description: Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 16 participants 16 participants 32 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
1
   6.3%
1
   3.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
   6.3%
0
   0.0%
1
   3.1%
White
15
  93.8%
15
  93.8%
30
  93.8%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Analysis Population Description: Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Weight   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 16 participants 16 participants 32 participants
72.03  (9.012) 68.73  (8.859) 70.38  (8.949)
[1]
Measure Analysis Population Description: Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Height   [1] 
Mean (Standard Deviation)
Unit of measure:  Cm
Number Analyzed 16 participants 16 participants 32 participants
168.41  (6.966) 167.31  (7.684) 167.86  (7.236)
[1]
Measure Analysis Population Description: Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Body Mass Index   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 16 participants 16 participants 32 participants
25.38  (2.806) 24.52  (2.341) 24.95  (2.579)
[1]
Measure Analysis Population Description: Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Duration of Diabetes   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 16 participants 16 participants 32 participants
27.81  (13.177) 21.94  (10.866) 24.88  (12.249)
[1]
Measure Analysis Population Description: Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Current Administration of Insulin   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
CSII Number Analyzed 16 participants 16 participants 32 participants
10
  62.5%
11
  68.8%
21
  65.6%
MDI Number Analyzed 16 participants 16 participants 32 participants
4
  25.0%
5
  31.3%
9
  28.1%
Both Number Analyzed 16 participants 16 participants 32 participants
2
  12.5%
0
   0.0%
2
   6.3%
[1]
Measure Description: Subject's usual method of insulin administration - either multiple daily injections (MDI) or continuous subcutaneous infusion of insulin (CSII), or both.
[2]
Measure Analysis Population Description: Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Renal Status Category   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
<30 mL/min Number Analyzed 16 participants 16 participants 32 participants
0
   0.0%
0
   0.0%
0
   0.0%
≥30 to <60 mL/min Number Analyzed 16 participants 16 participants 32 participants
2
  12.5%
0
   0.0%
2
   6.3%
≥60 to <90 mL/min Number Analyzed 16 participants 16 participants 32 participants
8
  50.0%
8
  50.0%
16
  50.0%
≥90 mL/min Number Analyzed 16 participants 16 participants 32 participants
6
  37.5%
8
  50.0%
14
  43.8%
[1]
Measure Analysis Population Description: Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Baseline Fasting Glucose   [1] 
Mean (Standard Deviation)
Unit of measure:  mmol/L
Number Analyzed 15 participants 16 participants 31 participants
8.57  (2.767) 8.15  (3.149) 8.35  (2.928)
[1]
Measure Analysis Population Description: Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Baseline A1c   [1] 
Mean (Standard Deviation)
Unit of measure:  %
Number Analyzed 16 participants 16 participants 32 participants
7.84  (0.356) 8.21  (0.574) 8.03  (0.506)
[1]
Measure Analysis Population Description: Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Baseline C-peptide   [1] 
Mean (Standard Deviation)
Unit of measure:  nmol/L
Number Analyzed 1 participants 2 participants 3 participants
0.030  (0) 0.030  (0.0141) 0.030  (0.0100)
[1]
Measure Analysis Population Description: Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Baseline Insulin   [1] 
Mean (Standard Deviation)
Unit of measure:  U/day
Number Analyzed 16 participants 16 participants 32 participants
38.14  (12.525) 36.58  (8.920) 37.36  (10.725)
[1]
Measure Analysis Population Description: Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
1.Primary Outcome
Title Efficacy of Pramlintide by Measurement of 24-hour Tissue Mean Weighted Glucose (MWG) Obtained With Continuous Glucose Monitoring (CGM)
Hide Description 24-hour MWG mg/dL, defined as total area under the 24-hour tissue glucose curve obtained with CGM, divided by actual time span in the 24-hour period.
Time Frame 24 h
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: Of the 33 correctly randomized subjects, 26 (76.5%) had at least 1 efficacy assessment available from each of the 2 crossover periods and were included in the Full Analysis Set.
Arm/Group Title Placebo & Regular Insulin Pramlintide & Regular Insulin
Hide Arm/Group Description:
Placebo was similar sterile solution without pramlintide
Pramlintide was administered by sc infusion at a concentration of 1000ug/ml
Overall Number of Participants Analyzed 26 26
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
173.8  (8.17) 152.2  (8.17)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo & Regular Insulin, Pramlintide & Regular Insulin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0118
Comments [Not Specified]
Method Linear mixed-effects model
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -21.5
Confidence Interval (2-Sided) 95%
-37.8 to -5.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 7.88
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Efficacy of Pramlintide by Measurement of Absolute Plasma Glucose Area Under the Plasma Concentration-time Curve (AUC) Following Lunch
Hide Description Absolute postprandial plasma glucose AUC was measured for the first 3 hours (AUC0-3h) following lunch based on sample availability. (Sample times: 20 hours [lunch], 20 hours 45 min, 21 hours, 23 hours, 24 hours).
Time Frame 3 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic/Pharmacodynamic (PK/PD) Analysis Set: Of the 33 correctly randomized subjects, 26 (76.5%) subjects received at least 1 dose of pramlintide and had evaluable PD data and were, therefore, included in the PK/PD Analysis Set.
Arm/Group Title Placebo & Regular Insulin Pramlintide & Regular Insulin
Hide Arm/Group Description:
Placebo was similar sterile solution without pramlintide
Pramlintide was administered by sc infusion at a concentration of 1000ug/ml
Overall Number of Participants Analyzed 25 24
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mmol/L*h
36.233
(31.427 to 41.039)
28.336
(23.487 to 33.185)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo & Regular Insulin, Pramlintide & Regular Insulin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0013
Comments [Not Specified]
Method Linear mixed effects model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference (pramlintide-placebo)
Estimated Value -7.897
Confidence Interval (2-Sided) 95%
-12.356 to -3.438
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Efficacy of Pramlintide by Measurement of Absolute Plasma Glucose Area Under the Plasma Concentration-time Curve (AUC) Following Dinner
Hide Description Absolute postprandial plasma glucose AUC (AUC0-2h) was measured for the first 2 hours following dinner based on sample availability. (Sample times: 2 hours [dinner], 2 hours 45 min, 3 hours, 4 hours).
Time Frame 2 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic/Pharmacodynamic (PK/PD) Analysis Set: Of the 33 correctly randomized subjects, 26 (76.5%) subjects received at least 1 dose of pramlintide and had evaluable PD data and were, therefore, included in the PK/PD Analysis Set.
Arm/Group Title Placebo & Regular Insulin Pramlintide & Regular Insulin
Hide Arm/Group Description:
Placebo was similar sterile solution without pramlintide
Pramlintide was administered by sc infusion at a concentration of 1000ug/ml
Overall Number of Participants Analyzed 25 26
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mmol/L*h
23.247
(20.472 to 26.021)
17.970
(15.231 to 20.709)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo & Regular Insulin, Pramlintide & Regular Insulin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0091
Comments [Not Specified]
Method Linear mixed effects model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference (pramlintide-placebo)
Estimated Value -5.277
Confidence Interval (2-Sided) 95%
-9.175 to -1.378
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Efficacy of Pramlintide by Measurement of Absolute Plasma Glucose Area Under the Plasma Concentration-time Curve (AUC) Following Breakfast
Hide Description Absolute postprandial plasma glucose AUC (AUC0-2h) was measured for the first 2 hours following breakfast based on sample availability. (Sample times: 16 hours [breakfast], 16 hours 45 min, 17 hours, 18 hours).
Time Frame 2 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic/Pharmacodynamic (PK/PD) Analysis Set: Of the 33 correctly randomized subjects, 26 (76.5%) subjects received at least 1 dose of pramlintide and had evaluable PD data and were, therefore, included in the PK/PD Analysis Set.
Arm/Group Title Placebo & Regular Insulin Pramlintide & Regular Insulin
Hide Arm/Group Description:
Placebo was similar sterile solution without pramlintide
Pramlintide was administered by sc infusion at a concentration of 1000ug/ml
Overall Number of Participants Analyzed 26 24
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mmol/L*h
23.535
(20.817 to 26.253)
19.101
(16.280 to 21.922)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo & Regular Insulin, Pramlintide & Regular Insulin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0057
Comments [Not Specified]
Method Linear mixed effects model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference (pramlintide-placebo)
Estimated Value -4.435
Confidence Interval (2-Sided) 95%
-7.445 to -1.424
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Efficacy of Pramlintide by Measurement of Incremental 24-hour Tissue Glucose Area Under the Plasma Concentration-time Curve (AUC) Obtained With Continuous Glucose Monitoring (CGM)
Hide Description Incremental (i.e., baseline-corrected) area under the 24-hour tissue glucose concentration curve (AUC0-24h) measured by continuous glucose monitoring (CGM) with a pre-test, non-fasting tissue glucose value as baseline. (Sample times: 0, 30 min, 2 hours [dinner], 2 hours 45 min, 3 hours, 4 hours, 9 hours, 12 hours, 14 hours, 16 hours [breakfast], 16 hours 45 min, 17 hours, 18 hours, 20 hours [lunch], 20 hours 45 min, 21 hours, 23 hours, 24 hours).
Time Frame 24 h
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: Of the 33 correctly randomized subjects, 26 (76.5%) had at least 1 efficacy assessment available from each of the 2 crossover periods and were included in the Full Analysis Set,
Arm/Group Title Placebo & Regular Insulin Pramlintide & Regular Insulin
Hide Arm/Group Description:
Placebo was similar sterile solution without pramlintide
Pramlintide was administered by sc infusion at a concentration of 1000ug/ml
Overall Number of Participants Analyzed 26 26
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL*min
26243  (3379.8) -2489  (3379.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo & Regular Insulin, Pramlintide & Regular Insulin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Linear mixed-effects model
Comments [Not Specified]
Method of Estimation Estimation Parameter Least squares mean difference
Estimated Value -28733
Confidence Interval (2-Sided) 95%
-37326 to -20139
Parameter Dispersion
Type: Standard Error of the Mean
Value: 4163.6
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Efficacy of Pramlintide by Measurement of Absolute 24-hour Plasma Glucose Area Under the Plasma Concentration-time Curve (AUC)
Hide Description Absolute mean area under the 24-hour plasma glucose concentration curve, measured as total area under the curve (0 to 24 hours). (Sample times: 0, 30 min, 2 hours [dinner], 2 hours 45 min, 3 hours, 4 hours, 9 hours, 12 hours, 14 hours, 16 hours [breakfast], 16 hours 45 min, 17 hours, 18 hours, 20 hours [lunch], 20 hours 45 min, 21 hours, 23 hours, 24 hours).
Time Frame 24 h
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic/Pharmacodynamic (PK/PD) Analysis Set: Of the 33 correctly randomized subjects, 26 (76.5%) subjects received at least 1 dose of pramlintide and had evaluable PD data and were, therefore, included in the PK/PD Analysis Set.
Arm/Group Title Placebo & Regular Insulin Pramlintide & Regular Insulin
Hide Arm/Group Description:
Placebo was similar sterile solution without pramlintide
Pramlintide was administered by sc infusion at a concentration of 1000ug/ml
Overall Number of Participants Analyzed 26 26
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mmol/L*h
243.835
(220.032 to 267.638)
215.417
(191.614 to 239.220)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo & Regular Insulin, Pramlintide & Regular Insulin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0258
Comments [Not Specified]
Method Linear mixed-effects model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -28.418
Confidence Interval (2-Sided) 95%
-53.099 to -3.737
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Efficacy of Pramlintide by Measurement of Incremental 24-hour Plasma Glucose Area Under the Plasma Concentration-time Curve (AUC)
Hide Description Incremental (i.e., baseline-corrected) mean area under the 24-hour plasma glucose concentration curve, measured as total area under the curve (0 to 24 hours). (Sample times: 0, 30 min, 2 hours [dinner], 2 hours 45 min, 3 hours, 4 hours, 9 hours, 12 hours, 14 hours, 16 hours [breakfast], 16 hours 45 min, 17 hours, 18 hours, 20 hours [lunch], 20 hours 45 min, 21 hours, 23 hours, 24 hours).
Time Frame 24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic/Pharmacodynamic (PK/PD) Analysis Set: Of the 33 correctly randomized subjects, 26 (76.5%) subjects received at least 1 dose of pramlintide and had evaluable PD data and were, therefore, included in the PK/PD Analysis Set.
Arm/Group Title Placebo & Regular Insulin Pramlintide & Regular Insulin
Hide Arm/Group Description:
Placebo was similar sterile solution without pramlintide
Pramlintide was administered by sc infusion at a concentration of 1000ug/ml
Overall Number of Participants Analyzed 26 26
Mean (Standard Deviation)
Unit of Measure: mmol/L*h
11.181  (67.6648) -12.753  (70.0174)
8.Secondary Outcome
Title Efficacy of Pramlintide Measured by Percent Time Spent in the Range of >70 mg/dL to <180 mg/dL Tissue Glucose Obtained With Continuous Glucose Monitoring (CGM)
Hide Description Percent time spent in the normoglycemic range of tissue glucose concentrations between >70 mg/dL and <180 mg/dL, measured by CGM. (Sample times: 0, 30 min, 2 hours [dinner], 2 hours 45 min, 3 hours, 4 hours, 9 hours, 12 hours, 14 hours, 16 hours [breakfast], 16 hours 45 min, 17 hours, 18 hours, 20 hours [lunch], 20 hours 45 min, 21 hours, 23 hours, 24 hours).
Time Frame 24 h
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set:Of the 33 correctly randomized subjects, 26 (76.5%) had at least 1 efficacy assessment available from each of the 2 crossover periods and were included in the Full Analysis Set.
Arm/Group Title Placebo & Regular Insulin Pramlintide & Regular Insulin
Hide Arm/Group Description:
Placebo was similar sterile solution without pramlintide
Pramlintide was administered by sc infusion at a concentration of 1000ug/ml
Overall Number of Participants Analyzed 26 26
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Percentage of time
43.8
(33.6 to 56.9)
57.2
(44.0 to 74.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo & Regular Insulin, Pramlintide & Regular Insulin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0456
Comments [Not Specified]
Method Linear mixed-effects model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Ratio (Pramlintide/Placebo)
Estimated Value 1.31
Confidence Interval (2-Sided) 95%
1.01 to 1.70
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Efficacy of Pramlintide by Measurement of Absolute 24-hour Plasma Glucagon Area Under the Plasma Concentration-time Curve (AUC)
Hide Description Absolute mean area under the 24-hour plasma glucagon concentration curve, measured as total area under the curve (total AUC0-24). (Sample times: 0, 30 min, 2 hours [dinner], 2 hours 45 min, 3 hours, 4 hours, 9 hours, 12 hours, 14 hours, 16 hours [breakfast], 16 hours 45 min, 17 hours, 18 hours, 20 hours [lunch], 20 hours 45 min, 21 hours, 23 hours, 24 hours).
Time Frame 24 h
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic/Pharmacodynamic (PK/PD) Analysis Set: Of the 33 correctly randomized subjects, 26 (76.5%) subjects received at least 1 dose of pramlintide and had evaluable PD data and were, therefore, included in the PK/PD Analysis Set.
Arm/Group Title Placebo & Regular Insulin Pramlintide & Regular Insulin
Hide Arm/Group Description:
Placebo was similar sterile solution without pramlintide
Pramlintide was administered by sc infusion at a concentration of 1000ug/ml
Overall Number of Participants Analyzed 26 26
Least Squares Mean (95% Confidence Interval)
Unit of Measure: h*pmol/L
506.265
(459.096 to 558.280)
481.633
(436.759 to 531.118)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo & Regular Insulin, Pramlintide & Regular Insulin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1015
Comments [Not Specified]
Method Linear mixed-effects model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean ratio (pramlintide/placebo)
Estimated Value 0.951
Confidence Interval (2-Sided) 95%
0.896 to 1.011
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Efficacy of Pramlintide by Measurement of Incremental 24-hour Plasma Glucagon Area Under the Plasma Concentration-time Curve (AUC)
Hide Description Incremental (i.e., baseline-corrected) mean area under the 24-hour plasma glucagon concentration curve with a pre-test, non-fasting plasma glucagon value as baseline. (Sample times: 0, 30 min, 2 hours [dinner], 2 hours 45 min, 3 hours, 4 hours, 9 hours, 12 hours, 14 hours, 16 hours [breakfast], 16 hours 45 min, 17 hours, 18 hours, 20 hours [lunch], 20 hours 45 min, 21 hours, 23 hours, 24 hours).
Time Frame 24 h
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic/Pharmacodynamic (PK/PD) Analysis Set: Of the 33 correctly randomized subjects, 26 (76.5%) subjects received at least 1 dose of pramlintide and had evaluable PD data and were, therefore, included in the PK/PD Analysis Set.
Arm/Group Title Placebo & Regular Insulin Pramlintide & Regular Insulin
Hide Arm/Group Description:
Placebo was similar sterile solution without pramlintide
Pramlintide was administered by sc infusion at a concentration of 1000ug/ml
Overall Number of Participants Analyzed 26 26
Mean (Standard Deviation)
Unit of Measure: pmol/L*h
-14.954  (58.9024) -16.055  (69.2684)
11.Secondary Outcome
Title Fasting Plasma Glucose Concentration
Hide Description Fasting plasma glucose concentration at 0600 hours (6:00 AM)
Time Frame 12 hours after dinner meal
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic/Pharmacodynamic (PK/PD) Analysis Set: Of the 33 correctly randomized subjects, 26 (76.5%) subjects received at least 1 dose of pramlintide and had evaluable PD data and were, therefore, included in the PK/PD Analysis Set.
Arm/Group Title Placebo & Regular Insulin Pramlintide & Regular Insulin
Hide Arm/Group Description:
Placebo was similar sterile solution without pramlintide
Pramlintide was administered by sc infusion at a concentration of 1000ug/ml
Overall Number of Participants Analyzed 26 26
Least Squares Mean (95% Confidence Interval)
Unit of Measure: mmol/L
7.794
(6.631 to 9.162)
8.459
(7.196 to 9.943)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo & Regular Insulin, Pramlintide & Regular Insulin
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3730
Comments [Not Specified]
Method Linear mixed effects model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean ratio (pramlintide/placebo)
Estimated Value 1.085
Confidence Interval (2-Sided) 95%
0.901 to 1.307
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Pharmacokinetics of Insulin as Demonstrated by 24-hour Plasma Insulin Area Under the Plasma Concentration-time Curve (AUC)
Hide Description Mean areas under the plasma insulin concentration curves for the 24-hour periods of pramlintide and placebo administration (Sample times: -15 min, 0, 30 min, 1 hour 30 min, 2 hours [dinner], 2 hours 15 min, 2 hours 30 min, 2 hours 45 min, 3 hours, 4 hours, 5 hours, 6 hours, 9 hours, 12 hours, 15 hours, 16 hours [breakfast], 16 hours 15 min, 16 hours 30 min, 16 hours 45 min, 17 hours, 18 hours, 19 hours, 20 hours [lunch], 24 hours).
Time Frame 24 hours
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Hide Analysis Population Description
Pharmacokinetic/Pharmacodynamic (PK/PD) Analysis Set: Of the 33 correctly randomized subjects, 26 (76.5%) subjects received at least 1 dose of pramlintide and had evaluable PD data and were, therefore, included in the PK/PD Analysis Set.
Arm/Group Title Placebo & Regular Insulin Pramlintide & Regular Insulin
Hide Arm/Group Description:
Placebo was similar sterile solution without pramlintide
Pramlintide was administered by sc infusion at a concentration of 1000ug/ml
Overall Number of Participants Analyzed 26 26
Mean (Standard Deviation)
Unit of Measure: mU/L*h
380.525  (178.2360) 377.324  (176.7569)
13.Secondary Outcome
Title Pharmacokinetics of Insulin as Demonstrated by 24-hour Average Plasma Insulin Concentration.
Hide Description Mean values of the average plasma insulin concentrations over the 24-hour periods of pramlintide and placebo administration. (Sample times: -15 min, 0, 30 min, 1 hour 30 min, 2 hours [dinner], 2 hours 15 min, 2 hours 30 min, 2 hours 45 min, 3 hours, 4 hours, 5 hours, 6 hours, 9 hours, 12 hours, 15 hours, 16 hours [breakfast], 16 hours 15 min, 16 hours 30 min, 16 hours 45 min, 17 hours, 18 hours, 19 hours, 20 hours [lunch], 24 hours).
Time Frame 24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic/Pharmacodynamic (PK/PD) Analysis Set: Of the 33 correctly randomized subjects, 26 (76.5%) subjects received at least 1 dose of pramlintide and had evaluable PD data and were, therefore, included in the PK/PD Analysis Set.
Arm/Group Title Placebo & Regular Insulin Pramlintide & Regular Insulin
Hide Arm/Group Description:
Placebo was similar sterile solution without pramlintide
Pramlintide was administered by sc infusion at a concentration of 1000ug/ml
Overall Number of Participants Analyzed 26 26
Mean (Standard Deviation)
Unit of Measure: mIU/L
15.855  (7.4265) 15.722  (7.3649)
14.Secondary Outcome
Title Pharmacokinetics of Insulin as Demonstrated by Maximum Plasma Insulin Concentration
Hide Description Mean maximum plasma insulin concentrations over the 24-hour periods of pramlintide and placebo administration. (Sample times: -15 min, 0, 30 min, 1 hour 30 min, 2 hours [dinner], 2 hours 15 min, 2 hours 30 min, 2 hours 45 min, 3 hours, 4 hours, 5 hours, 6 hours, 9 hours, 12 hours, 15 hours, 16 hours [breakfast], 16 hours 15 min, 16 hours 30 min, 16 hours 45 min, 17 hours, 18 hours, 19 hours, 20 hours [lunch], 24 hours).
Time Frame 24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic/Pharmacodynamic (PK/PD) Analysis Set: Of the 33 correctly randomized subjects, 26 (76.5%) subjects received at least 1 dose of pramlintide and had evaluable PD data and were, therefore, included in the PK/PD Analysis Set.
Arm/Group Title Placebo & Regular Insulin Pramlintide & Regular Insulin
Hide Arm/Group Description:
Placebo was similar sterile solution without pramlintide
Pramlintide was administered by sc infusion at a concentration of 1000ug/ml
Overall Number of Participants Analyzed 26 26
Mean (Standard Deviation)
Unit of Measure: mIU/L
33.144  (17.0950) 32.838  (16.2315)
15.Secondary Outcome
Title Pharmacokinetics of Insulin as Demonstrated by the Time to the Maximum Plasma Insulin Concentration
Hide Description Mean time to maximum plasma insulin concentrations over the 24-hour periods of pramlintide and placebo administration. (Sample times: -15 min, 0, 30 min, 1 hour 30 min, 2 hours [dinner], 2 hours 15 min, 2 hours 30 min, 2 hours 45 min, 3 hours, 4 hours, 5 hours, 6 hours, 9 hours, 12 hours, 15 hours, 16 hours [breakfast], 16 hours 15 min, 16 hours 30 min, 16 hours 45 min, 17 hours, 18 hours, 19 hours, 20 hours [lunch], 24 hours).
Time Frame 24 hours
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic/Pharmacodynamic (PK/PD) Analysis Set: Of the 33 correctly randomized subjects, 26 (76.5%) subjects received at least 1 dose of pramlintide and had evaluable PD data and were, therefore, included in the PK/PD Analysis Set.
Arm/Group Title Placebo & Regular Insulin Pramlintide & Regular Insulin
Hide Arm/Group Description:
Placebo was similar sterile solution without pramlintide
Pramlintide was administered by sc infusion at a concentration of 1000ug/ml
Overall Number of Participants Analyzed 26 26
Mean (Standard Deviation)
Unit of Measure: h
10.556  (7.3466) 11.653  (7.6175)
Time Frame Over two 24-hour treatment periods with a 2-week washout period between periods.
Adverse Event Reporting Description This was a crossover study.
 
Arm/Group Title Placebo & Regular Insulin Pramlintide & Regular Insulin
Hide Arm/Group Description Placebo was similar sterile solution without pramlintide Pramlintide was administered by sc infusion at a concentration of 1000ug/ml
All-Cause Mortality
Placebo & Regular Insulin Pramlintide & Regular Insulin
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Placebo & Regular Insulin Pramlintide & Regular Insulin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/28 (0.00%)      0/32 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Placebo & Regular Insulin Pramlintide & Regular Insulin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/28 (32.14%)      22/32 (68.75%)    
Blood and lymphatic system disorders     
Anaemia  1  4/28 (14.29%)  4 0/32 (0.00%)  0
Cardiac disorders     
Cardiovascular disorder  1  0/28 (0.00%)  0 1/32 (3.13%)  1
Eye disorders     
Vitreous Detachment  1  1/28 (3.57%)  1 0/32 (0.00%)  0
Gastrointestinal disorders     
Vomiting  1  0/28 (0.00%)  0 6/32 (18.75%)  6
Nausea  1  2/28 (7.14%)  2 14/32 (43.75%)  14
Abdominal discomfort  1  0/28 (0.00%)  0 1/32 (3.13%)  1
General disorders     
Fatigue  1  0/28 (0.00%)  0 1/32 (3.13%)  1
Infections and infestations     
Gastroenteritis  1  0/28 (0.00%)  0 1/32 (3.13%)  1
Nasopharyngitis  1  1/28 (3.57%)  1 0/32 (0.00%)  0
Urinary tract infection  1  0/28 (0.00%)  0 1/32 (3.13%)  1
Injury, poisoning and procedural complications     
Contusion  1  1/28 (3.57%)  1 0/32 (0.00%)  0
Metabolism and nutrition disorders     
Dehydration  1  0/28 (0.00%)  0 1/32 (3.13%)  1
Hypoglycaemia  1  0/28 (0.00%)  0 3/32 (9.38%)  4
Musculoskeletal and connective tissue disorders     
Pain in extremity  1  0/28 (0.00%)  0 1/32 (3.13%)  1
Nervous system disorders     
Tremor  1  2/28 (7.14%)  3 1/32 (3.13%)  1
Headache  1  1/28 (3.57%)  1 8/32 (25.00%)  9
Psychiatric disorders     
Anxiety  1  1/28 (3.57%)  1 0/32 (0.00%)  0
Irritability  1  1/28 (3.57%)  1 0/32 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Sinus congestion  1  0/28 (0.00%)  0 1/32 (3.13%)  1
Skin and subcutaneous tissue disorders     
Ecchymosis  1  1/28 (3.57%)  1 0/32 (0.00%)  0
Hyperhidrosis  1  1/28 (3.57%)  1 0/32 (0.00%)  0
Photosensitivity reaction  1  0/28 (0.00%)  0 1/32 (3.13%)  1
Pruritus  1  0/28 (0.00%)  0 1/32 (3.13%)  1
Pruritus allergic  1  1/28 (3.57%)  1 0/32 (0.00%)  0
Scab  1  0/28 (0.00%)  0 1/32 (3.13%)  1
Vascular disorders     
Phlebitis  1  1/28 (3.57%)  1 0/32 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA v.19.0
Due to the unavailability of the pramlintide assay, no data are presented for pramlintide PK parameters, and changes in pramlintide concentration could not be related to changes in insulin, plasma glucose, glucagon, or triglycerides.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Peter Ohman
Organization: AstraZeneca
Phone: +1 (301) 398-0120
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT02500979     History of Changes
Other Study ID Numbers: D5570C00002
First Submitted: July 10, 2015
First Posted: July 17, 2015
Results First Submitted: August 2, 2017
Results First Posted: November 2, 2018
Last Update Posted: November 2, 2018