Trial Outcomes & Findings for Effect of a Fixed Pramlintide: Insulin Dose Ratio on Postprandial Glucose in Type 1 Diabetes Mellitus (NCT NCT02500979)

Last Updated: 2018-11-02

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

34 participants

Primary outcome timeframe

24 h

Results posted on

2018-11-02

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Pramlintide First, Then Placebo (Treatment Sequence A)	Placebo First, Then Pramlintide (Treatment Sequence B)
Period 1 STARTED	16	17
Period 1 COMPLETED	12	16
Period 1 NOT COMPLETED	4	1
Period 2 STARTED	12	16
Period 2 COMPLETED	11	16
Period 2 NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Pramlintide First, Then Placebo (Treatment Sequence A)	Placebo First, Then Pramlintide (Treatment Sequence B)
Period 1 Hyperglycemia	1	0
Period 1 Severe non-compliance to protocol	0	1
Period 1 Adverse Event	1	0
Period 1 Subject decision	2	0
Period 2 Change in risk	1	0

Baseline Characteristics

Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: 24 h

Population: 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.

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.

Outcome measures

Outcome measures
Measure	Placebo & Regular Insulin n=26 Participants Placebo was similar sterile solution without pramlintide	Pramlintide & Regular Insulin n=26 Participants Pramlintide was administered by sc infusion at a concentration of 1000ug/ml
Efficacy of Pramlintide by Measurement of 24-hour Tissue Mean Weighted Glucose (MWG) Obtained With Continuous Glucose Monitoring (CGM)	173.8 mg/dL Standard Error 8.17	152.2 mg/dL Standard Error 8.17

SECONDARY outcome

Timeframe: 3 hours

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Placebo & Regular Insulin n=25 Participants Placebo was similar sterile solution without pramlintide	Pramlintide & Regular Insulin n=24 Participants Pramlintide was administered by sc infusion at a concentration of 1000ug/ml
Efficacy of Pramlintide by Measurement of Absolute Plasma Glucose Area Under the Plasma Concentration-time Curve (AUC) Following Lunch	36.233 mmol/L*h Interval 31.427 to 41.039	28.336 mmol/L*h Interval 23.487 to 33.185

SECONDARY outcome

Timeframe: 2 hours

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).

Outcome measures

Outcome measures
Measure	Placebo & Regular Insulin n=25 Participants Placebo was similar sterile solution without pramlintide	Pramlintide & Regular Insulin n=26 Participants Pramlintide was administered by sc infusion at a concentration of 1000ug/ml
Efficacy of Pramlintide by Measurement of Absolute Plasma Glucose Area Under the Plasma Concentration-time Curve (AUC) Following Dinner	23.247 mmol/L*h Interval 20.472 to 26.021	17.970 mmol/L*h Interval 15.231 to 20.709

SECONDARY outcome

Timeframe: 2 hours

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).

Outcome measures

Outcome measures
Measure	Placebo & Regular Insulin n=26 Participants Placebo was similar sterile solution without pramlintide	Pramlintide & Regular Insulin n=24 Participants Pramlintide was administered by sc infusion at a concentration of 1000ug/ml
Efficacy of Pramlintide by Measurement of Absolute Plasma Glucose Area Under the Plasma Concentration-time Curve (AUC) Following Breakfast	23.535 mmol/L*h Interval 20.817 to 26.253	19.101 mmol/L*h Interval 16.28 to 21.922

SECONDARY outcome

Timeframe: 24 h

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).

Outcome measures

Outcome measures
Measure	Placebo & Regular Insulin n=26 Participants Placebo was similar sterile solution without pramlintide	Pramlintide & Regular Insulin n=26 Participants Pramlintide was administered by sc infusion at a concentration of 1000ug/ml
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)	26243 mg/dL*min Standard Error 3379.8	-2489 mg/dL*min Standard Error 3379.8

SECONDARY outcome

Timeframe: 24 h

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).

Outcome measures

Outcome measures
Measure	Placebo & Regular Insulin n=26 Participants Placebo was similar sterile solution without pramlintide	Pramlintide & Regular Insulin n=26 Participants Pramlintide was administered by sc infusion at a concentration of 1000ug/ml
Efficacy of Pramlintide by Measurement of Absolute 24-hour Plasma Glucose Area Under the Plasma Concentration-time Curve (AUC)	243.835 mmol/L*h Interval 220.032 to 267.638	215.417 mmol/L*h Interval 191.614 to 239.22

SECONDARY outcome

Timeframe: 24 hours

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).

Outcome measures

Outcome measures
Measure	Placebo & Regular Insulin n=26 Participants Placebo was similar sterile solution without pramlintide	Pramlintide & Regular Insulin n=26 Participants Pramlintide was administered by sc infusion at a concentration of 1000ug/ml
Efficacy of Pramlintide by Measurement of Incremental 24-hour Plasma Glucose Area Under the Plasma Concentration-time Curve (AUC)	11.181 mmol/L*h Standard Deviation 67.6648	-12.753 mmol/L*h Standard Deviation 70.0174

SECONDARY outcome

Timeframe: 24 h

Population: 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.

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).

Outcome measures

Outcome measures
Measure	Placebo & Regular Insulin n=26 Participants Placebo was similar sterile solution without pramlintide	Pramlintide & Regular Insulin n=26 Participants Pramlintide was administered by sc infusion at a concentration of 1000ug/ml
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)	43.8 Percentage of time Interval 33.6 to 56.9	57.2 Percentage of time Interval 44.0 to 74.4

SECONDARY outcome

Timeframe: 24 h

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).

Outcome measures

Outcome measures
Measure	Placebo & Regular Insulin n=26 Participants Placebo was similar sterile solution without pramlintide	Pramlintide & Regular Insulin n=26 Participants Pramlintide was administered by sc infusion at a concentration of 1000ug/ml
Efficacy of Pramlintide by Measurement of Absolute 24-hour Plasma Glucagon Area Under the Plasma Concentration-time Curve (AUC)	506.265 h*pmol/L Interval 459.096 to 558.28	481.633 h*pmol/L Interval 436.759 to 531.118

SECONDARY outcome

Timeframe: 24 h

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).

Outcome measures

Outcome measures
Measure	Placebo & Regular Insulin n=26 Participants Placebo was similar sterile solution without pramlintide	Pramlintide & Regular Insulin n=26 Participants Pramlintide was administered by sc infusion at a concentration of 1000ug/ml
Efficacy of Pramlintide by Measurement of Incremental 24-hour Plasma Glucagon Area Under the Plasma Concentration-time Curve (AUC)	-14.954 pmol/L*h Standard Deviation 58.9024	-16.055 pmol/L*h Standard Deviation 69.2684

SECONDARY outcome

Timeframe: 12 hours after dinner meal

Fasting plasma glucose concentration at 0600 hours (6:00 AM)

Outcome measures

Outcome measures
Measure	Placebo & Regular Insulin n=26 Participants Placebo was similar sterile solution without pramlintide	Pramlintide & Regular Insulin n=26 Participants Pramlintide was administered by sc infusion at a concentration of 1000ug/ml
Fasting Plasma Glucose Concentration	7.794 mmol/L Interval 6.631 to 9.162	8.459 mmol/L Interval 7.196 to 9.943

SECONDARY outcome

Timeframe: 24 hours

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).

Outcome measures

Outcome measures
Measure	Placebo & Regular Insulin n=26 Participants Placebo was similar sterile solution without pramlintide	Pramlintide & Regular Insulin n=26 Participants Pramlintide was administered by sc infusion at a concentration of 1000ug/ml
Pharmacokinetics of Insulin as Demonstrated by 24-hour Plasma Insulin Area Under the Plasma Concentration-time Curve (AUC)	380.525 mU/L*h Standard Deviation 178.2360	377.324 mU/L*h Standard Deviation 176.7569

SECONDARY outcome

Timeframe: 24 hours

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).

Outcome measures

Outcome measures
Measure	Placebo & Regular Insulin n=26 Participants Placebo was similar sterile solution without pramlintide	Pramlintide & Regular Insulin n=26 Participants Pramlintide was administered by sc infusion at a concentration of 1000ug/ml
Pharmacokinetics of Insulin as Demonstrated by 24-hour Average Plasma Insulin Concentration.	15.855 mIU/L Standard Deviation 7.4265	15.722 mIU/L Standard Deviation 7.3649

SECONDARY outcome

Timeframe: 24 hours

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).

Outcome measures

Outcome measures
Measure	Placebo & Regular Insulin n=26 Participants Placebo was similar sterile solution without pramlintide	Pramlintide & Regular Insulin n=26 Participants Pramlintide was administered by sc infusion at a concentration of 1000ug/ml
Pharmacokinetics of Insulin as Demonstrated by Maximum Plasma Insulin Concentration	33.144 mIU/L Standard Deviation 17.0950	32.838 mIU/L Standard Deviation 16.2315

SECONDARY outcome

Timeframe: 24 hours

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).

Outcome measures

Outcome measures
Measure	Placebo & Regular Insulin n=26 Participants Placebo was similar sterile solution without pramlintide	Pramlintide & Regular Insulin n=26 Participants Pramlintide was administered by sc infusion at a concentration of 1000ug/ml
Pharmacokinetics of Insulin as Demonstrated by the Time to the Maximum Plasma Insulin Concentration	10.556 h Standard Deviation 7.3466	11.653 h Standard Deviation 7.6175

Adverse Events

Placebo & Regular Insulin

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Pramlintide & Regular Insulin

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Peter Ohman

AstraZeneca

Phone: +1 (301) 398-0120

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Pramlintide First, Then Placebo n=16 Participants (Treatment Sequence A) - Safety Analysis Set	Placebo First, Then Pramlintide n=16 Participants (Treatment Sequence B) - Safety Analysis Set	Total n=32 Participants Total of all reporting groups
Current Administration of Insulin MDI	4 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	5 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	9 Participants n=32 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Age, Categorical <=18 years	0 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	0 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	0 Participants n=32 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Age, Categorical Between 18 and 65 years	14 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	16 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	30 Participants n=32 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Age, Categorical >=65 years	2 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	0 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	2 Participants n=32 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Age, Continuous	45.1 Years STANDARD_DEVIATION 14.83 • n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	38.9 Years STANDARD_DEVIATION 12.68 • n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	42.0 Years STANDARD_DEVIATION 13.92 • n=32 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Sex: Female, Male Female	13 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	12 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	25 Participants n=32 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Sex: Female, Male Male	3 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	4 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	7 Participants n=32 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	2 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	2 Participants n=32 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Ethnicity (NIH/OMB) Not Hispanic or Latino	16 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	14 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	30 Participants n=32 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	0 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	0 Participants n=32 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	0 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	0 Participants n=32 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Race (NIH/OMB) Asian	0 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	1 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	1 Participants n=32 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	0 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	0 Participants n=32 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Race (NIH/OMB) Black or African American	1 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	0 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	1 Participants n=32 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Race (NIH/OMB) White	15 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	15 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	30 Participants n=32 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Race (NIH/OMB) More than one race	0 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	0 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	0 Participants n=32 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	0 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	0 Participants n=32 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Weight	72.03 kg STANDARD_DEVIATION 9.012 • n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	68.73 kg STANDARD_DEVIATION 8.859 • n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	70.38 kg STANDARD_DEVIATION 8.949 • n=32 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Height	168.41 cm STANDARD_DEVIATION 6.966 • n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	167.31 cm STANDARD_DEVIATION 7.684 • n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	167.86 cm STANDARD_DEVIATION 7.236 • n=32 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Body Mass Index	25.38 kg/m^2 STANDARD_DEVIATION 2.806 • n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	24.52 kg/m^2 STANDARD_DEVIATION 2.341 • n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	24.95 kg/m^2 STANDARD_DEVIATION 2.579 • n=32 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Duration of Diabetes	27.81 Years STANDARD_DEVIATION 13.177 • n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	21.94 Years STANDARD_DEVIATION 10.866 • n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	24.88 Years STANDARD_DEVIATION 12.249 • n=32 Participants • 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 CSII	10 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	11 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	21 Participants n=32 Participants • 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 Both	2 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	0 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	2 Participants n=32 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Renal Status Category <30 mL/min	0 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	0 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	0 Participants n=32 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Renal Status Category ≥30 to <60 mL/min	2 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	0 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	2 Participants n=32 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Renal Status Category ≥60 to <90 mL/min	8 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	8 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	16 Participants n=32 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Renal Status Category ≥90 mL/min	6 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	8 Participants n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	14 Participants n=32 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Baseline Fasting Glucose	8.57 mmol/L STANDARD_DEVIATION 2.767 • n=15 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	8.15 mmol/L STANDARD_DEVIATION 3.149 • n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	8.35 mmol/L STANDARD_DEVIATION 2.928 • n=31 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Baseline A1c	7.84 % STANDARD_DEVIATION 0.356 • n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	8.21 % STANDARD_DEVIATION 0.574 • n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	8.03 % STANDARD_DEVIATION 0.506 • n=32 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Baseline C-peptide	0.030 nmol/L STANDARD_DEVIATION 0 • n=1 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	0.030 nmol/L STANDARD_DEVIATION 0.0141 • n=2 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	0.030 nmol/L STANDARD_DEVIATION 0.0100 • n=3 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.
Baseline Insulin	38.14 U/day STANDARD_DEVIATION 12.525 • n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	36.58 U/day STANDARD_DEVIATION 8.920 • n=16 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.	37.36 U/day STANDARD_DEVIATION 10.725 • n=32 Participants • Safety Analysis Set: All randomized subjects receiving any infused study treatment. Subjects were analyzed according to the treatment sequence they received.

Measure	Placebo & Regular Insulin n=28 participants at risk Placebo was similar sterile solution without pramlintide	Pramlintide & Regular Insulin n=32 participants at risk Pramlintide was administered by sc infusion at a concentration of 1000ug/ml
Blood and lymphatic system disorders Anaemia	14.3% 4/28 • Number of events 4 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.	0.00% 0/32 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.
Gastrointestinal disorders Vomiting	0.00% 0/28 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.	18.8% 6/32 • Number of events 6 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.
Gastrointestinal disorders Nausea	7.1% 2/28 • Number of events 2 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.	43.8% 14/32 • Number of events 14 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.
Cardiac disorders Cardiovascular disorder	0.00% 0/28 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.	3.1% 1/32 • Number of events 1 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.
Eye disorders Vitreous Detachment	3.6% 1/28 • Number of events 1 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.	0.00% 0/32 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/28 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.	3.1% 1/32 • Number of events 1 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.
General disorders Fatigue	0.00% 0/28 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.	3.1% 1/32 • Number of events 1 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.
Infections and infestations Gastroenteritis	0.00% 0/28 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.	3.1% 1/32 • Number of events 1 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.
Infections and infestations Nasopharyngitis	3.6% 1/28 • Number of events 1 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.	0.00% 0/32 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.
Infections and infestations Urinary tract infection	0.00% 0/28 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.	3.1% 1/32 • Number of events 1 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.
Injury, poisoning and procedural complications Contusion	3.6% 1/28 • Number of events 1 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.	0.00% 0/32 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.
Metabolism and nutrition disorders Dehydration	0.00% 0/28 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.	3.1% 1/32 • Number of events 1 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/28 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.	9.4% 3/32 • Number of events 4 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/28 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.	3.1% 1/32 • Number of events 1 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.
Nervous system disorders Tremor	7.1% 2/28 • Number of events 3 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.	3.1% 1/32 • Number of events 1 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.
Nervous system disorders Headache	3.6% 1/28 • Number of events 1 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.	25.0% 8/32 • Number of events 9 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.
Psychiatric disorders Anxiety	3.6% 1/28 • Number of events 1 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.	0.00% 0/32 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.
Psychiatric disorders Irritability	3.6% 1/28 • Number of events 1 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.	0.00% 0/32 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.
Respiratory, thoracic and mediastinal disorders Sinus congestion	0.00% 0/28 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.	3.1% 1/32 • Number of events 1 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.
Skin and subcutaneous tissue disorders Ecchymosis	3.6% 1/28 • Number of events 1 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.	0.00% 0/32 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.
Skin and subcutaneous tissue disorders Hyperhidrosis	3.6% 1/28 • Number of events 1 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.	0.00% 0/32 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.
Skin and subcutaneous tissue disorders Photosensitivity reaction	0.00% 0/28 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.	3.1% 1/32 • Number of events 1 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/28 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.	3.1% 1/32 • Number of events 1 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.
Skin and subcutaneous tissue disorders Pruritus allergic	3.6% 1/28 • Number of events 1 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.	0.00% 0/32 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.
Skin and subcutaneous tissue disorders Scab	0.00% 0/28 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.	3.1% 1/32 • Number of events 1 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.
Vascular disorders Phlebitis	3.6% 1/28 • Number of events 1 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.	0.00% 0/32 • Over two 24-hour treatment periods with a 2-week washout period between periods. This was a crossover study.