Trial Outcomes & Findings for Safety Study of Subcutaneously-Injected Prandial INSULIN-PH20 NP Compared to Insulin Lispro Injection in Participants With Type 1 Diabetes Mellitus (NCT NCT00883558)
NCT ID: NCT00883558
Last Updated: 2014-09-08
Results Overview
A 2-hour postprandial glucose excursion was measured for 3 meals over 3 days during each treatment cycle (3 days during Week 14 of the first treatment cycle and 3 days during Week 26 of the second treatment cycle). For each of the 3 days, the mealtime (breakfast, lunch, and dinner) excursions were calculated as the post-meal glucose value minus the pre-meal value as determined by 8-point glucose monitoring. The average of all excursions over the 3 days for the corresponding treatment cycle is presented.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
48 participants
Primary outcome timeframe
Week 14 and Week 26
Results posted on
2014-09-08
Participant Flow
Participant milestones
| Measure |
All Enrolled Participants
Prior to randomization, all enrolled participants underwent a 1-month dose titration period.
Insulin Lispro (Titration Period): 100 units per milliliter (U/mL), injected subcutaneously before meals, with doses titrated to each individual participant's glycemic control needs, for 1 month.
Participants requiring basal insulin used twice daily, subcutaneous injections of 100 U/mL insulin glargine or maintained their usual regimen through an infusion pump.
|
INSULIN-PH20 NP First, Then Insulin Lispro
Following a 1-month dose titration period, participants were randomly assigned to Treatment A for the first 3-month treatment cycle, followed by Treatment B for the second 3-month treatment cycle.
INSULIN-PH20 NP (Treatment A): 100 units per milliliter (U/mL) non-preserved (NP) formulation of recombinant human insulin with 5.0 micrograms per milliliter (µg/mL) recombinant human hyaluronidase PH20, injected subcutaneously before meals, with doses titrated to each individual participant's glycemic control needs, for 3 months.
Insulin Lispro (Treatment B): 100 U/mL insulin lispro, injected subcutaneously before meals, with doses titrated to each individual participant's glycemic control needs, for 3 months.
Participants requiring basal insulin used twice daily, subcutaneous injections of 100 U/mL insulin glargine or maintained their usual regimen through an infusion pump.
|
Insulin Lispro First, Then INSULIN-PH20 NP
Following a 1-month dose titration period, participants were randomly assigned to Treatment B for the first 3-month treatment cycle, followed by Treatment A for the second 3-month treatment cycle.
Insulin Lispro (Treatment B): 100 units per milliliter (U/mL) insulin lispro, injected subcutaneously before meals, with doses titrated to each individual participant's glycemic control needs, for 3 months.
INSULIN-PH20 NP (Treatment A): 100 U/mL non-preserved (NP) formulation of recombinant human insulin with 5.0 micrograms per milliliter (µg/mL) recombinant human hyaluronidase PH20, injected subcutaneously before meals, with doses titrated to each individual participant's glycemic control needs, for 3 months.
Participants requiring basal insulin used twice daily, subcutaneous injections of 100 U/mL insulin glargine or maintained their usual regimen through an infusion pump.
|
|---|---|---|---|
|
Titration Period (Weeks 0 to 4)
STARTED
|
48
|
0
|
0
|
|
Titration Period (Weeks 0 to 4)
COMPLETED
|
46
|
0
|
0
|
|
Titration Period (Weeks 0 to 4)
NOT COMPLETED
|
2
|
0
|
0
|
|
First Treatment Cycle (Weeks 4 to 16)
STARTED
|
0
|
22
|
24
|
|
First Treatment Cycle (Weeks 4 to 16)
Received at Least 1 Dose of Study Drug
|
0
|
22
|
24
|
|
First Treatment Cycle (Weeks 4 to 16)
COMPLETED
|
0
|
19
|
23
|
|
First Treatment Cycle (Weeks 4 to 16)
NOT COMPLETED
|
0
|
3
|
1
|
|
Second Treatment Cycle (Weeks 16 to 28)
STARTED
|
0
|
19
|
23
|
|
Second Treatment Cycle (Weeks 16 to 28)
Received at Least 1 Dose of Study Drug
|
0
|
19
|
23
|
|
Second Treatment Cycle (Weeks 16 to 28)
COMPLETED
|
0
|
19
|
22
|
|
Second Treatment Cycle (Weeks 16 to 28)
NOT COMPLETED
|
0
|
0
|
1
|
Reasons for withdrawal
| Measure |
All Enrolled Participants
Prior to randomization, all enrolled participants underwent a 1-month dose titration period.
Insulin Lispro (Titration Period): 100 units per milliliter (U/mL), injected subcutaneously before meals, with doses titrated to each individual participant's glycemic control needs, for 1 month.
Participants requiring basal insulin used twice daily, subcutaneous injections of 100 U/mL insulin glargine or maintained their usual regimen through an infusion pump.
|
INSULIN-PH20 NP First, Then Insulin Lispro
Following a 1-month dose titration period, participants were randomly assigned to Treatment A for the first 3-month treatment cycle, followed by Treatment B for the second 3-month treatment cycle.
INSULIN-PH20 NP (Treatment A): 100 units per milliliter (U/mL) non-preserved (NP) formulation of recombinant human insulin with 5.0 micrograms per milliliter (µg/mL) recombinant human hyaluronidase PH20, injected subcutaneously before meals, with doses titrated to each individual participant's glycemic control needs, for 3 months.
Insulin Lispro (Treatment B): 100 U/mL insulin lispro, injected subcutaneously before meals, with doses titrated to each individual participant's glycemic control needs, for 3 months.
Participants requiring basal insulin used twice daily, subcutaneous injections of 100 U/mL insulin glargine or maintained their usual regimen through an infusion pump.
|
Insulin Lispro First, Then INSULIN-PH20 NP
Following a 1-month dose titration period, participants were randomly assigned to Treatment B for the first 3-month treatment cycle, followed by Treatment A for the second 3-month treatment cycle.
Insulin Lispro (Treatment B): 100 units per milliliter (U/mL) insulin lispro, injected subcutaneously before meals, with doses titrated to each individual participant's glycemic control needs, for 3 months.
INSULIN-PH20 NP (Treatment A): 100 U/mL non-preserved (NP) formulation of recombinant human insulin with 5.0 micrograms per milliliter (µg/mL) recombinant human hyaluronidase PH20, injected subcutaneously before meals, with doses titrated to each individual participant's glycemic control needs, for 3 months.
Participants requiring basal insulin used twice daily, subcutaneous injections of 100 U/mL insulin glargine or maintained their usual regimen through an infusion pump.
|
|---|---|---|---|
|
Titration Period (Weeks 0 to 4)
Withdrawal by Subject
|
2
|
0
|
0
|
|
First Treatment Cycle (Weeks 4 to 16)
Adverse Event
|
0
|
1
|
0
|
|
First Treatment Cycle (Weeks 4 to 16)
Withdrawal by Subject
|
0
|
1
|
1
|
|
First Treatment Cycle (Weeks 4 to 16)
Protocol Violation
|
0
|
1
|
0
|
|
Second Treatment Cycle (Weeks 16 to 28)
Withdrawal by Subject
|
0
|
0
|
1
|
Baseline Characteristics
Safety Study of Subcutaneously-Injected Prandial INSULIN-PH20 NP Compared to Insulin Lispro Injection in Participants With Type 1 Diabetes Mellitus
Baseline characteristics by cohort
| Measure |
All Randomized Participants
n=46 Participants
Following a 1-month titration period, participants were randomly assigned to 1 of 2 study treatments (Treatment A or B) for the first of two, 3-month treatment cycles. Each participant then received the second treatment for the second cycle.
INSULIN-PH20 NP (Treatment A): 100 U/mL non-preserved (NP) formulation of regular human insulin with 5.0 micrograms per milliliter (µg/mL) recombinant human hyaluronidase PH20, injected SC, pre-meals, doses titrated to each participant individually.
Insulin Lispro (Treatment B): 100 U/mL insulin lispro, injected SC, pre-meals, doses titrated to each participant individually.
Throughout the study, participants requiring basal insulin used twice daily SC injections of 100 U/mL insulin glargine or maintained their usual regimen through an insulin pump.
|
|---|---|
|
Age, Continuous
|
41.6 years
STANDARD_DEVIATION 13.28 • n=5 Participants
|
|
Sex: Female, Male
Female
|
22 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
24 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
44 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
44 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
46 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 14 and Week 26Population: Participants who completed both treatment cycles with evaluable postprandial glucose data.
A 2-hour postprandial glucose excursion was measured for 3 meals over 3 days during each treatment cycle (3 days during Week 14 of the first treatment cycle and 3 days during Week 26 of the second treatment cycle). For each of the 3 days, the mealtime (breakfast, lunch, and dinner) excursions were calculated as the post-meal glucose value minus the pre-meal value as determined by 8-point glucose monitoring. The average of all excursions over the 3 days for the corresponding treatment cycle is presented.
Outcome measures
| Measure |
INSULIN-PH20 NP
n=37 Participants
100 units per milliliter (U/mL) non-preserved formulation of recombinant human insulin with 5.0 micrograms per milliliter (µg/mL) recombinant human hyaluronidase (INSULIN-PH20 NP), injected subcutaneously before meals, with doses titrated to each individual participant's glycemic control needs, for 3 months.
|
Insulin Lispro
n=37 Participants
100 units per milliliter (U/mL) insulin lispro, injected subcutaneously before meals, with doses titrated to each individual participant's glycemic control needs, for 3 months.
|
|---|---|---|
|
Postprandial Glucose Excursion
|
17.23 milligrams per deciliter (mg/dL)
Standard Deviation 36.040
|
14.47 milligrams per deciliter (mg/dL)
Standard Deviation 35.113
|
SECONDARY outcome
Timeframe: Week 14 and Week 26Population: Participants that completed both treatment cycles with evaluable CGM data.
Participants were provided a continuous glucose monitoring (CGM) device, consisting of a sensor, transmitter, and receiver. Total time the participant's blood glucose was outside the 71-139 mg/dL range during 3 days of CGM during each treatment cycle (3 days during Week 14 of the first treatment cycle and 3 days during Week 26 of the second treatment cycle) is presented.
Outcome measures
| Measure |
INSULIN-PH20 NP
n=40 Participants
100 units per milliliter (U/mL) non-preserved formulation of recombinant human insulin with 5.0 micrograms per milliliter (µg/mL) recombinant human hyaluronidase (INSULIN-PH20 NP), injected subcutaneously before meals, with doses titrated to each individual participant's glycemic control needs, for 3 months.
|
Insulin Lispro
n=40 Participants
100 units per milliliter (U/mL) insulin lispro, injected subcutaneously before meals, with doses titrated to each individual participant's glycemic control needs, for 3 months.
|
|---|---|---|
|
Time Spent With Blood Glucose Value Outside a 71-139 Milligrams Per Deciliter (mg/dL) Range During Continuous Glucose Monitoring
|
14.58 hours
Standard Deviation 3.155
|
13.37 hours
Standard Deviation 3.933
|
SECONDARY outcome
Timeframe: Baseline through Week 29Population: Participants who received at least 1 dose of study drug.
The number of participants with at least one hypoglycemic event (HE) reported during the entire study is presented. Additionally, the number of participants with severe HEs (those that necessitated administration of carbohydrate or glucagon, or resuscitation, by another person) is also presented. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.
Outcome measures
| Measure |
INSULIN-PH20 NP
n=45 Participants
100 units per milliliter (U/mL) non-preserved formulation of recombinant human insulin with 5.0 micrograms per milliliter (µg/mL) recombinant human hyaluronidase (INSULIN-PH20 NP), injected subcutaneously before meals, with doses titrated to each individual participant's glycemic control needs, for 3 months.
|
Insulin Lispro
n=43 Participants
100 units per milliliter (U/mL) insulin lispro, injected subcutaneously before meals, with doses titrated to each individual participant's glycemic control needs, for 3 months.
|
|---|---|---|
|
Number of Participants With Hypoglycemic Events
Severe HE
|
2 participants
|
0 participants
|
|
Number of Participants With Hypoglycemic Events
Overall
|
45 participants
|
43 participants
|
Adverse Events
INSULIN-PH20 NP Treatment Period
Serious events: 2 serious events
Other events: 17 other events
Deaths: 0 deaths
Insulin Lispro Treatment Period
Serious events: 1 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
INSULIN-PH20 NP Treatment Period
n=45 participants at risk
100 units per milliliter (U/mL) non-preserved formulation of recombinant human insulin with 5.0 micrograms per milliliter (µg/mL) recombinant human hyaluronidase (INSULIN-PH20 NP), injected subcutaneously before meals, with doses titrated to each individual participant's glycemic control needs, for 3 months.
|
Insulin Lispro Treatment Period
n=43 participants at risk
100 units per milliliter (U/mL) insulin lispro, injected subcutaneously before meals, with doses titrated to each individual participant's glycemic control needs, for 3 months.
|
|---|---|---|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc degeneration
|
2.2%
1/45 • Number of events 1 • An adverse event was considered treatment-emergent if the start date of the event was on or after the date of randomization.
|
0.00%
0/43 • An adverse event was considered treatment-emergent if the start date of the event was on or after the date of randomization.
|
|
Reproductive system and breast disorders
Uterine haemorrhage
|
4.5%
1/22 • Number of events 1 • An adverse event was considered treatment-emergent if the start date of the event was on or after the date of randomization.
|
0.00%
0/20 • An adverse event was considered treatment-emergent if the start date of the event was on or after the date of randomization.
|
|
Injury, poisoning and procedural complications
Haemothorax
|
0.00%
0/45 • An adverse event was considered treatment-emergent if the start date of the event was on or after the date of randomization.
|
2.3%
1/43 • Number of events 1 • An adverse event was considered treatment-emergent if the start date of the event was on or after the date of randomization.
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.00%
0/45 • An adverse event was considered treatment-emergent if the start date of the event was on or after the date of randomization.
|
2.3%
1/43 • Number of events 1 • An adverse event was considered treatment-emergent if the start date of the event was on or after the date of randomization.
|
Other adverse events
| Measure |
INSULIN-PH20 NP Treatment Period
n=45 participants at risk
100 units per milliliter (U/mL) non-preserved formulation of recombinant human insulin with 5.0 micrograms per milliliter (µg/mL) recombinant human hyaluronidase (INSULIN-PH20 NP), injected subcutaneously before meals, with doses titrated to each individual participant's glycemic control needs, for 3 months.
|
Insulin Lispro Treatment Period
n=43 participants at risk
100 units per milliliter (U/mL) insulin lispro, injected subcutaneously before meals, with doses titrated to each individual participant's glycemic control needs, for 3 months.
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
15.6%
7/45 • Number of events 7 • An adverse event was considered treatment-emergent if the start date of the event was on or after the date of randomization.
|
16.3%
7/43 • Number of events 8 • An adverse event was considered treatment-emergent if the start date of the event was on or after the date of randomization.
|
|
Infections and infestations
Upper respiratory tract infection
|
2.2%
1/45 • Number of events 1 • An adverse event was considered treatment-emergent if the start date of the event was on or after the date of randomization.
|
7.0%
3/43 • Number of events 3 • An adverse event was considered treatment-emergent if the start date of the event was on or after the date of randomization.
|
|
Infections and infestations
Sinusitis
|
4.4%
2/45 • Number of events 2 • An adverse event was considered treatment-emergent if the start date of the event was on or after the date of randomization.
|
2.3%
1/43 • Number of events 1 • An adverse event was considered treatment-emergent if the start date of the event was on or after the date of randomization.
|
|
Infections and infestations
Bronchitis
|
4.4%
2/45 • Number of events 2 • An adverse event was considered treatment-emergent if the start date of the event was on or after the date of randomization.
|
0.00%
0/43 • An adverse event was considered treatment-emergent if the start date of the event was on or after the date of randomization.
|
|
Infections and infestations
Fungal infection
|
4.4%
2/45 • Number of events 2 • An adverse event was considered treatment-emergent if the start date of the event was on or after the date of randomization.
|
2.3%
1/43 • Number of events 1 • An adverse event was considered treatment-emergent if the start date of the event was on or after the date of randomization.
|
|
Gastrointestinal disorders
Food poisoning
|
0.00%
0/45 • An adverse event was considered treatment-emergent if the start date of the event was on or after the date of randomization.
|
4.7%
2/43 • Number of events 2 • An adverse event was considered treatment-emergent if the start date of the event was on or after the date of randomization.
|
|
General disorders
Injection site haematoma
|
4.4%
2/45 • Number of events 3 • An adverse event was considered treatment-emergent if the start date of the event was on or after the date of randomization.
|
2.3%
1/43 • Number of events 1 • An adverse event was considered treatment-emergent if the start date of the event was on or after the date of randomization.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
6.7%
3/45 • Number of events 3 • An adverse event was considered treatment-emergent if the start date of the event was on or after the date of randomization.
|
0.00%
0/43 • An adverse event was considered treatment-emergent if the start date of the event was on or after the date of randomization.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/45 • An adverse event was considered treatment-emergent if the start date of the event was on or after the date of randomization.
|
4.7%
2/43 • Number of events 2 • An adverse event was considered treatment-emergent if the start date of the event was on or after the date of randomization.
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
4.4%
2/45 • Number of events 2 • An adverse event was considered treatment-emergent if the start date of the event was on or after the date of randomization.
|
0.00%
0/43 • An adverse event was considered treatment-emergent if the start date of the event was on or after the date of randomization.
|
|
Vascular disorders
Hypertension
|
4.4%
2/45 • Number of events 2 • An adverse event was considered treatment-emergent if the start date of the event was on or after the date of randomization.
|
0.00%
0/43 • An adverse event was considered treatment-emergent if the start date of the event was on or after the date of randomization.
|
Additional Information
Vice President, Endocrinology Clinical Development
Halozyme Therapeutics, Inc.
Phone: 858-794-8889
Results disclosure agreements
- Principal investigator is a sponsor employee All information obtained as a result of this study or during the conduct of this study will be regarded as confidential. The investigator agrees to use the information for the purpose of carrying out this study and for no other purpose, unless written permission from the sponsor (Halozyme) is obtained.
- Publication restrictions are in place
Restriction type: OTHER