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Study of Human Plasma-Derived Alpha1-Proteinase Inhibitor in Subjects With New-Onset Type 1 Diabetes Mellitus

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02093221
Recruitment Status : Terminated (Wk 52 primary endpoint results would be unaffected by follow-up data so trial was discontinued prior to wk 104. No safety data was collected after wk 52.)
First Posted : March 20, 2014
Results First Posted : April 19, 2018
Last Update Posted : September 5, 2018
Sponsor:
Information provided by (Responsible Party):
Grifols Therapeutics LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Type 1 Diabetes Mellitus
Interventions Biological: 180 mg/kg Alpha1-PI
Biological: 90 mg/kg Alpha1-PI
Biological: Placebo
Enrollment 76
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Alpha1-PI 180 mg/kg/wk, 26 Weeks 180 mg/kg/wk Alpha1-PI, 13 Weeks 90 mg/kg/wk Alpha1-PI, 26 Weeks 90 mg/kg/wk Alpha1-PI, 13 Weeks Placebo
Hide Arm/Group Description

180 mg/kg weekly infusions of Alpha1-PI for 26 weeks.

180 mg/kg Alpha1-PI

180 mg/kg weekly infusions of Alpha1-PI for 13 weeks.

180 mg/kg Alpha1-PI

90 mg/kg weekly infusions of Alpha1-PI for 26 weeks.

90 mg/kg Alpha1-PI

90 mg/kg weekly infusions of Alpha1-PI for 13 weeks

90 mg/kg Alpha1-PI

Weekly infusions of placebo for 13 or 26 weeks.

Placebo

Period Title: Overall Study
Started 15 16 15 15 15
Completed 5 8 6 7 7
Not Completed 10 8 9 8 8
Reason Not Completed
Adverse Event             1             0             0             0             0
Withdrawal by Subject             1             1             4             1             1
Lost to Follow-up             2             0             1             1             0
Death             0             1             0             0             0
Protocol Violation             0             1             0             0             0
Study termination             6             5             4             6             7
Arm/Group Title Alpha1-PI 180 mg/kg/wk, 26 Weeks 180 mg/kg/wk Alpha1-PI, 13 Weeks 90 mg/kg/wk Alpha1-PI, 26 Weeks 90 mg/kg/wk Alpha1-PI, 13 Weeks Placebo Total
Hide Arm/Group Description

180 mg/kg weekly infusions of Alpha1-PI for 26 weeks.

180 mg/kg Alpha1-PI

180 mg/kg weekly infusions of Alpha1-PI for 13 weeks.

180 mg/kg Alpha1-PI

90 mg/kg weekly infusions of Alpha1-PI for 26 weeks.

90 mg/kg Alpha1-PI

90 mg/kg weekly infusions of Alpha1-PI for 13 weeks

90 mg/kg Alpha1-PI

Weekly infusions of placebo for 13 or 26 weeks.

Placebo

Total of all reporting groups
Overall Number of Baseline Participants 15 16 15 15 15 76
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 16 participants 15 participants 15 participants 15 participants 76 participants
6 - 11 years
2
  13.3%
3
  18.8%
3
  20.0%
3
  20.0%
2
  13.3%
13
  17.1%
12 - 17 years
7
  46.7%
7
  43.8%
7
  46.7%
7
  46.7%
6
  40.0%
34
  44.7%
18 - 35 years
6
  40.0%
6
  37.5%
5
  33.3%
5
  33.3%
7
  46.7%
29
  38.2%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 16 participants 15 participants 15 participants 15 participants 76 participants
Female
6
  40.0%
8
  50.0%
9
  60.0%
4
  26.7%
4
  26.7%
31
  40.8%
Male
9
  60.0%
8
  50.0%
6
  40.0%
11
  73.3%
11
  73.3%
45
  59.2%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 16 participants 15 participants 15 participants 15 participants 76 participants
Hispanic or Latino
3
  20.0%
1
   6.3%
3
  20.0%
2
  13.3%
0
   0.0%
9
  11.8%
Not Hispanic or Latino
12
  80.0%
15
  93.8%
12
  80.0%
13
  86.7%
15
 100.0%
67
  88.2%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 16 participants 15 participants 15 participants 15 participants 76 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
1
   6.3%
0
   0.0%
2
  13.3%
0
   0.0%
3
   3.9%
White
14
  93.3%
14
  87.5%
15
 100.0%
13
  86.7%
15
 100.0%
71
  93.4%
More than one race
1
   6.7%
1
   6.3%
0
   0.0%
0
   0.0%
0
   0.0%
2
   2.6%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Change From Baseline in Mixed Meal Tolerance Test (MMTMT) Stimulated C-peptide 2 Hour Area Under the Concentration-time Curve (AUC)
Hide Description C-peptide concentration during MMTT with high protein energy drink. "Dose" for time frame refers to intake of high protein energy drink.
Time Frame Baseline, Week 52 (pre-high protein drink and 15, 30, 60, 90, 120 minutes post-drink)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Twelve subjects prematurely discontinued from the study prior to Week 52.
Arm/Group Title Alpha1-PI 180 mg/kg/wk, 26 Weeks 180 mg/kg/wk Alpha1-PI, 13 Weeks 90 mg/kg/wk Alpha1-PI, 26 Weeks 90 mg/kg/wk Alpha1-PI, 13 Weeks Placebo
Hide Arm/Group Description:

180 mg/kg weekly infusions of Alpha1-PI for 26 weeks.

180 mg/kg Alpha1-PI

180 mg/kg weekly infusions of Alpha1-PI for 13 weeks.

180 mg/kg Alpha1-PI

90 mg/kg weekly infusions of Alpha1-PI for 26 weeks.

90 mg/kg Alpha1-PI

90 mg/kg weekly infusions of Alpha1-PI for 13 weeks

90 mg/kg Alpha1-PI

Weekly infusions of placebo for 13 or 26 weeks.

Placebo

Overall Number of Participants Analyzed 13 14 11 12 14
Mean (Standard Deviation)
Unit of Measure: min*nmol/L
-32.357  (27.7184) -25.171  (28.9450) -21.682  (24.5787) -34.393  (25.6837) -16.909  (19.1278)
2.Secondary Outcome
Title Change From Baseline for MMTT Stimulated C-peptide 2h AUC
Hide Description [Not Specified]
Time Frame Baseline, Weeks 14, 27, 39, 69, 87, and 104 (pre-high protein drink and 15, 30, 60, 90, 120 minutes post-drink)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Forty-three subjects prematurely discontinued (prior to Week 104); 28 subjects were considered a premature discontinuation due to sponsor termination of the study.
Arm/Group Title Alpha1-PI 180 mg/kg/wk, 26 Weeks 180 mg/kg/wk Alpha1-PI, 13 Weeks 90 mg/kg/wk Alpha1-PI, 26 Weeks 90 mg/kg/wk Alpha1-PI, 13 Weeks Placebo
Hide Arm/Group Description:

180 mg/kg weekly infusions of Alpha1-PI for 26 weeks.

180 mg/kg Alpha1-PI

180 mg/kg weekly infusions of Alpha1-PI for 13 weeks.

180 mg/kg Alpha1-PI

90 mg/kg weekly infusions of Alpha1-PI for 26 weeks.

90 mg/kg Alpha1-PI

90 mg/kg weekly infusions of Alpha1-PI for 13 weeks

90 mg/kg Alpha1-PI

Weekly infusions of placebo for 13 or 26 weeks.

Placebo

Overall Number of Participants Analyzed 15 16 15 15 15
Mean (Standard Deviation)
Unit of Measure: min*nmol/L
Week 14 Number Analyzed 12 participants 13 participants 14 participants 14 participants 14 participants
-19.396  (23.7789) -0.444  (18.8595) 4.427  (33.2220) -12.725  (20.2051) 3.317  (21.1784)
Week 27 Number Analyzed 12 participants 12 participants 13 participants 13 participants 13 participants
-30.709  (21.2821) -17.826  (21.0462) 6.537  (56.1336) -23.082  (22.3027) -1.411  (26.8550)
Week 39 Number Analyzed 10 participants 10 participants 10 participants 12 participants 12 participants
-28.500  (37.6682) -17.664  (26.1729) -23.342  (21.6945) -36.580  (20.7765) -10.808  (20.0078)
Week 69 Number Analyzed 10 participants 11 participants 9 participants 13 participants 14 participants
-45.316  (27.1563) -42.014  (15.7239) -27.023  (28.6920) -39.735  (23.3488) -16.744  (21.8947)
Week 87 Number Analyzed 7 participants 11 participants 7 participants 10 participants 9 participants
-42.487  (31.9418) -43.012  (23.2403) -34.590  (21.6148) -47.496  (23.7717) -32.561  (20.0826)
Week 104 Number Analyzed 5 participants 8 participants 5 participants 6 participants 7 participants
-29.687  (25.5941) -44.314  (28.0612) -32.980  (18.2765) -39.908  (26.4652) -26.586  (20.6803)
3.Secondary Outcome
Title Change From Baseline for HbA1c Levels
Hide Description [Not Specified]
Time Frame Baseline, Weeks 14, 27, 39, 52, 69, 87, and 104
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Forty-three subjects prematurely discontinued (prior to Week 104); 28 subjects were considered a premature discontinuation due to sponsor termination of the study.
Arm/Group Title Alpha1-PI 180 mg/kg/wk, 26 Weeks 180 mg/kg/wk Alpha1-PI, 13 Weeks 90 mg/kg/wk Alpha1-PI, 26 Weeks 90 mg/kg/wk Alpha1-PI, 13 Weeks Placebo
Hide Arm/Group Description:

180 mg/kg weekly infusions of Alpha1-PI for 26 weeks.

180 mg/kg Alpha1-PI

180 mg/kg weekly infusions of Alpha1-PI for 13 weeks.

180 mg/kg Alpha1-PI

90 mg/kg weekly infusions of Alpha1-PI for 26 weeks.

90 mg/kg Alpha1-PI

90 mg/kg weekly infusions of Alpha1-PI for 13 weeks

90 mg/kg Alpha1-PI

Weekly infusions of placebo for 13 or 26 weeks.

Placebo

Overall Number of Participants Analyzed 15 16 15 15 15
Mean (Standard Deviation)
Unit of Measure: percentage of change from baseline
Week 14 Number Analyzed 13 participants 13 participants 14 participants 13 participants 14 participants
-0.68  (2.108) -1.75  (2.543) -1.16  (1.683) -1.45  (1.812) -2.64  (2.452)
Week 27 Number Analyzed 13 participants 12 participants 14 participants 14 participants 13 participants
-0.67  (1.953) -1.38  (2.799) -0.74  (2.263) -0.89  (2.740) -2.52  (2.439)
Week 39 Number Analyzed 11 participants 12 participants 11 participants 13 participants 13 participants
-0.58  (2.098) -0.78  (3.043) -0.40  (1.495) -0.55  (2.798) -1.52  (2.473)
Week 52 Number Analyzed 13 participants 14 participants 11 participants 14 participants 14 participants
-0.47  (1.383) -0.55  (3.437) -0.25  (1.399) -0.51  (2.504) -1.52  (2.805)
Week 69 Number Analyzed 11 participants 13 participants 10 participants 13 participants 13 participants
-0.01  (1.630) -0.18  (2.529) 0.09  (1.197) -0.33  (2.532) -1.37  (3.004)
Week 87 Number Analyzed 7 participants 11 participants 8 participants 11 participants 9 participants
-0.54  (1.310) -0.38  (3.035) 0.30  (2.147) -0.26  (2.608) -0.89  (3.011)
Week 104 Number Analyzed 5 participants 8 participants 6 participants 7 participants 7 participants
-0.76  (1.419) -0.69  (2.490) 0.28  (1.987) -0.10  (2.890) -1.36  (2.155)
4.Secondary Outcome
Title Number of Subjects With Overall Severe Hypoglycemic Episodes
Hide Description Severe hypoglycemia defined according the ADA Workgroup on Hypoglycemia definition, as follows: An event requiring assistance of another person to actively administer carbohydrate, glucagons, or other resuscitative actions.
Time Frame 104 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Forty-three subjects prematurely discontinued (prior to Week 104); 28 subjects were considered a premature discontinuation due to sponsor termination of the study.
Arm/Group Title Alpha1-PI 180 mg/kg/wk, 26 Weeks 180 mg/kg/wk Alpha1-PI, 13 Weeks 90 mg/kg/wk Alpha1-PI, 26 Weeks 90 mg/kg/wk Alpha1-PI, 13 Weeks Placebo
Hide Arm/Group Description:

180 mg/kg weekly infusions of Alpha1-PI for 26 weeks.

180 mg/kg Alpha1-PI

180 mg/kg weekly infusions of Alpha1-PI for 13 weeks.

180 mg/kg Alpha1-PI

90 mg/kg weekly infusions of Alpha1-PI for 26 weeks.

90 mg/kg Alpha1-PI

90 mg/kg weekly infusions of Alpha1-PI for 13 weeks

90 mg/kg Alpha1-PI

Weekly infusions of placebo for 13 or 26 weeks.

Placebo

Overall Number of Participants Analyzed 15 16 15 15 15
Measure Type: Count of Participants
Unit of Measure: Participants
1 episode
1
   6.7%
2
  12.5%
0
   0.0%
0
   0.0%
1
   6.7%
2 episodes
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
3 episodes
0
   0.0%
0
   0.0%
1
   6.7%
0
   0.0%
0
   0.0%
5.Secondary Outcome
Title Change From Baseline for Mean Daily Insulin Dose Requirements
Hide Description [Not Specified]
Time Frame Baseline, Weeks 2, 4, 14, 27, 39, 52, 69, 87, and 104
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Forty-three subjects prematurely discontinued (prior to Week 104); 28 subjects were considered a premature discontinuation due to sponsor termination of the study.
Arm/Group Title Alpha1-PI 180 mg/kg/wk, 26 Weeks 180 mg/kg/wk Alpha1-PI, 13 Weeks 90 mg/kg/wk Alpha1-PI, 26 Weeks 90 mg/kg/wk Alpha1-PI, 13 Weeks Placebo
Hide Arm/Group Description:

180 mg/kg weekly infusions of Alpha1-PI for 26 weeks.

180 mg/kg Alpha1-PI

180 mg/kg weekly infusions of Alpha1-PI for 13 weeks.

180 mg/kg Alpha1-PI

90 mg/kg weekly infusions of Alpha1-PI for 26 weeks.

90 mg/kg Alpha1-PI

90 mg/kg weekly infusions of Alpha1-PI for 13 weeks

90 mg/kg Alpha1-PI

Weekly infusions of placebo for 13 or 26 weeks.

Placebo

Overall Number of Participants Analyzed 15 16 15 15 15
Mean (Standard Deviation)
Unit of Measure: U/kg/day
Week 2 Number Analyzed 8 participants 9 participants 7 participants 7 participants 9 participants
-0.146  (0.2044) -0.141  (0.2143) -0.205  (0.2194) -0.274  (0.1416) -0.158  (0.2828)
Week 4 Number Analyzed 8 participants 8 participants 9 participants 7 participants 8 participants
-0.147  (0.1405) -0.264  (0.1456) -0.201  (0.2058) -0.220  (0.1744) -0.150  (0.2788)
Week 14 Number Analyzed 9 participants 7 participants 7 participants 7 participants 8 participants
-0.239  (0.2301) -0.305  (0.1406) -0.092  (0.1442) -0.239  (0.1430) -0.118  (0.1114)
Week 27 Number Analyzed 5 participants 6 participants 8 participants 4 participants 5 participants
-0.040  (0.2313) -0.033  (0.4310) -0.090  (0.2117) -0.138  (0.2321) -0.135  (0.0607)
Week 39 Number Analyzed 3 participants 5 participants 8 participants 5 participants 4 participants
-0.040  (0.3222) 0.146  (0.7900) -0.089  (0.2099) -0.158  (0.2552) -0.150  (0.1100)
Week 52 Number Analyzed 5 participants 6 participants 8 participants 5 participants 4 participants
0.226  (0.5861) -0.037  (0.8720) -0.055  (0.2180) 0.214  (0.5898) -0.320  (0.2906)
Week 69 Number Analyzed 3 participants 6 participants 8 participants 6 participants 4 participants
0.192  (0.5491) 0.213  (0.6097) 0.142  (0.5981) 0.016  (0.7005) -0.011  (0.2858)
Week 87 Number Analyzed 1 participants 6 participants 6 participants 5 participants 2 participants
0.517  (0) 0.164  (0.5377) 0.247  (0.6591) 0.086  (0.5132) -0.044  (0.4264)
Week 104 Number Analyzed 1 participants 3 participants 4 participants 4 participants 1 participants
0.491  (0) -0.168  (0.4650) 0.307  (0.3772) -0.015  (0.5626) 0.303  (0)
6.Secondary Outcome
Title Change From Baseline for Mean Daily Glucose Levels Prior to Meals and Bedtime
Hide Description For each visit, the mean daily glucose levels were calculated over the previous 3-7 days prior to the study visit from blood glucose levels recorded daily prior to meals and bedtime.
Time Frame Baseline, Weeks 2, 4, 14, 27, 39, 52, 69, 87, and 104
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Forty-three subjects prematurely discontinued (prior to Week 104); 28 subjects were considered a premature discontinuation due to sponsor termination of the study.
Arm/Group Title Alpha1-PI 180 mg/kg/wk, 26 Weeks 180 mg/kg/wk Alpha1-PI, 13 Weeks 90 mg/kg/wk Alpha1-PI, 26 Weeks 90 mg/kg/wk Alpha1-PI, 13 Weeks Placebo
Hide Arm/Group Description:

180 mg/kg weekly infusions of Alpha1-PI for 26 weeks.

180 mg/kg Alpha1-PI

180 mg/kg weekly infusions of Alpha1-PI for 13 weeks.

180 mg/kg Alpha1-PI

90 mg/kg weekly infusions of Alpha1-PI for 26 weeks.

90 mg/kg Alpha1-PI

90 mg/kg weekly infusions of Alpha1-PI for 13 weeks

90 mg/kg Alpha1-PI

Weekly infusions of placebo for 13 or 26 weeks.

Placebo

Overall Number of Participants Analyzed 15 16 15 15 15
Mean (Standard Deviation)
Unit of Measure: mmol/L
Week 2 Number Analyzed 11 participants 12 participants 10 participants 11 participants 11 participants
2.223  (3.6282) 2.379  (2.7555) 1.848  (1.1257) 0.578  (1.6824) 0.178  (1.5195)
Week 4 Number Analyzed 11 participants 12 participants 10 participants 12 participants 11 participants
2.343  (2.3942) 1.856  (2.4750) 2.106  (1.3144) 0.759  (1.0403) -0.158  (1.4665)
Week 14 Number Analyzed 10 participants 9 participants 10 participants 13 participants 12 participants
2.812  (2.5953) 2.200  (2.1283) 2.852  (3.0376) 2.337  (3.9732) -0.053  (1.4368)
Week 27 Number Analyzed 7 participants 10 participants 9 participants 9 participants 9 participants
1.782  (1.7921) 2.252  (2.8173) 2.446  (3.2355) 3.471  (3.1043) 0.577  (2.1475)
Week 39 Number Analyzed 4 participants 9 participants 8 participants 8 participants 8 participants
1.347  (2.0674) 3.848  (2.2236) 4.471  (2.7390) 3.681  (4.0469) 1.421  (2.1779)
Week 52 Number Analyzed 7 participants 11 participants 9 participants 8 participants 8 participants
2.995  (1.6703) 3.067  (2.9160) 3.242  (3.1636) 2.723  (4.3749) 0.616  (2.1868)
Week 69 Number Analyzed 5 participants 10 participants 8 participants 6 participants 7 participants
2.182  (1.3352) 18.224  (41.1471) 4.324  (4.4173) 3.677  (3.7397) 1.467  (4.2254)
Week 87 Number Analyzed 2 participants 7 participants 7 participants 5 participants 2 participants
3.354  (2.9550) 3.101  (2.3859) 3.234  (2.1516) 3.835  (3.6760) 4.863  (2.5173)
Week 104 Number Analyzed 1 participants 4 participants 4 participants 4 participants 3 participants
2.545  (0) 1.867  (2.4532) 2.390  (1.5429) 2.283  (6.1064) 2.431  (1.4519)
Time Frame All AEs occurring after subject consent through Week 52 were collected
Adverse Event Reporting Description One subject in the 90 mg/kg/wk Alpha-1 PI, 26 Weeks group prematurely withdrew from the study, did not receive study drug, and was excluded from the safety population.
 
Arm/Group Title Alpha1-PI 180 mg/kg/wk, 26 Weeks 180 mg/kg/wk Alpha1-PI, 13 Weeks 90 mg/kg/wk Alpha1-PI, 26 Weeks 90 mg/kg/wk Alpha1-PI, 13 Weeks Placebo
Hide Arm/Group Description

180 mg/kg weekly infusions of Alpha1-PI for 26 weeks.

180 mg/kg Alpha1-PI

180 mg/kg weekly infusions of Alpha1-PI for 13 weeks.

180 mg/kg Alpha1-PI

90 mg/kg weekly infusions of Alpha1-PI for 26 weeks.

90 mg/kg Alpha1-PI

90 mg/kg weekly infusions of Alpha1-PI for 13 weeks

90 mg/kg Alpha1-PI

Weekly infusions of placebo for 13 or 26 weeks.

Placebo

All-Cause Mortality
Alpha1-PI 180 mg/kg/wk, 26 Weeks 180 mg/kg/wk Alpha1-PI, 13 Weeks 90 mg/kg/wk Alpha1-PI, 26 Weeks 90 mg/kg/wk Alpha1-PI, 13 Weeks Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/15 (0.00%)      1/16 (6.25%)      0/14 (0.00%)      0/15 (0.00%)      0/15 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Alpha1-PI 180 mg/kg/wk, 26 Weeks 180 mg/kg/wk Alpha1-PI, 13 Weeks 90 mg/kg/wk Alpha1-PI, 26 Weeks 90 mg/kg/wk Alpha1-PI, 13 Weeks Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/15 (0.00%)      3/16 (18.75%)      0/14 (0.00%)      0/15 (0.00%)      0/15 (0.00%)    
Metabolism and nutrition disorders           
Hyperglycaemia *  0/15 (0.00%)  0 1/16 (6.25%)  1 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Pregnancy, puerperium and perinatal conditions           
Abortion spontaneous *  0/15 (0.00%)  0 1/16 (6.25%)  1 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Psychiatric disorders           
Completed suicide *  0/15 (0.00%)  0 1/16 (6.25%)  1 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Alpha1-PI 180 mg/kg/wk, 26 Weeks 180 mg/kg/wk Alpha1-PI, 13 Weeks 90 mg/kg/wk Alpha1-PI, 26 Weeks 90 mg/kg/wk Alpha1-PI, 13 Weeks Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   10/15 (66.67%)      8/16 (50.00%)      11/14 (78.57%)      13/15 (86.67%)      11/15 (73.33%)    
Blood and lymphatic system disorders           
Lymphadenopathy *  1/15 (6.67%)  1 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Cardiac disorders           
Palpitations *  0/15 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 1/15 (6.67%)  1
Sinus arrhythmia *  0/15 (0.00%)  0 0/16 (0.00%)  0 1/14 (7.14%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0
Ear and labyrinth disorders           
Inner ear inflammation *  1/15 (6.67%)  1 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Endocrine disorders           
Hypothyroidism *  0/15 (0.00%)  0 1/16 (6.25%)  1 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Gastrointestinal disorders           
Abdominal discomfort *  0/15 (0.00%)  0 1/16 (6.25%)  1 1/14 (7.14%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0
Abdominal pain *  0/15 (0.00%)  0 0/16 (0.00%)  0 1/14 (7.14%)  1 0/15 (0.00%)  0 1/15 (6.67%)  1
Abdominal pain upper *  1/15 (6.67%)  1 2/16 (12.50%)  2 1/14 (7.14%)  1 1/15 (6.67%)  1 0/15 (0.00%)  0
Aphthous stomatitis *  0/15 (0.00%)  0 1/16 (6.25%)  1 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Constipation *  2/15 (13.33%)  2 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Diarrhoea *  0/15 (0.00%)  0 2/16 (12.50%)  2 1/14 (7.14%)  1 0/15 (0.00%)  0 1/15 (6.67%)  1
Gingival pain *  0/15 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0
Irritable bowel syndrome *  0/15 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 1/15 (6.67%)  1
Nausea *  1/15 (6.67%)  1 3/16 (18.75%)  3 1/14 (7.14%)  1 0/15 (0.00%)  0 2/15 (13.33%)  2
Tooth impacted *  0/15 (0.00%)  0 2/16 (12.50%)  2 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Vomiting *  2/15 (13.33%)  2 3/16 (18.75%)  4 0/14 (0.00%)  0 4/15 (26.67%)  4 1/15 (6.67%)  1
General disorders           
Chest discomfort *  0/15 (0.00%)  0 0/16 (0.00%)  0 1/14 (7.14%)  1 0/15 (0.00%)  0 1/15 (6.67%)  1
Fatigue *  0/15 (0.00%)  0 1/16 (6.25%)  2 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Feeling cold *  0/15 (0.00%)  0 1/16 (6.25%)  1 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Hypertrophy *  1/15 (6.67%)  1 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Infusion site bruising *  0/15 (0.00%)  0 0/16 (0.00%)  0 1/14 (7.14%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0
Infusion site extravasation *  0/15 (0.00%)  0 0/16 (0.00%)  0 1/14 (7.14%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0
Injection site bruising *  1/15 (6.67%)  1 1/16 (6.25%)  1 0/14 (0.00%)  0 0/15 (0.00%)  0 1/15 (6.67%)  1
Localised oedema *  0/15 (0.00%)  0 0/16 (0.00%)  0 1/14 (7.14%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0
Malaise *  1/15 (6.67%)  1 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Medical device complication *  0/15 (0.00%)  0 1/16 (6.25%)  1 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Non-cardiac chest pain *  0/15 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 1/15 (6.67%)  1 1/15 (6.67%)  1
Pain *  0/15 (0.00%)  0 1/16 (6.25%)  1 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Pyrexia *  0/15 (0.00%)  0 1/16 (6.25%)  2 0/14 (0.00%)  0 0/15 (0.00%)  0 1/15 (6.67%)  1
Vessel puncture site bruise *  0/15 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0
Immune system disorders           
Hypersensitivity *  0/15 (0.00%)  0 0/16 (0.00%)  0 1/14 (7.14%)  1 1/15 (6.67%)  1 0/15 (0.00%)  0
Multiple allergies *  0/15 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0
Seasonal allergy *  0/15 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0
Infections and infestations           
Cellulitis *  0/15 (0.00%)  0 0/16 (0.00%)  0 1/14 (7.14%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0
Croup infectious *  0/15 (0.00%)  0 0/16 (0.00%)  0 1/14 (7.14%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0
Fungal infection *  1/15 (6.67%)  1 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Gastroenteritis *  0/15 (0.00%)  0 2/16 (12.50%)  2 2/14 (14.29%)  2 0/15 (0.00%)  0 0/15 (0.00%)  0
Gastroenteritis viral *  0/15 (0.00%)  0 1/16 (6.25%)  1 1/14 (7.14%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0
Genitourinary tract infection *  1/15 (6.67%)  1 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Infectious mononucleosis *  0/15 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 1/15 (6.67%)  1
Influenza *  2/15 (13.33%)  2 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Nasopharyngitis *  2/15 (13.33%)  3 0/16 (0.00%)  0 3/14 (21.43%)  5 3/15 (20.00%)  4 2/15 (13.33%)  2
Onychomycosis *  1/15 (6.67%)  1 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Paronychia *  0/15 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 1/15 (6.67%)  1
Pharyngitis *  0/15 (0.00%)  0 1/16 (6.25%)  1 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Pharyngitis streptococcal *  0/15 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 1/15 (6.67%)  1
Rhinitis *  0/15 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 1/15 (6.67%)  2 0/15 (0.00%)  0
Sinusitis *  1/15 (6.67%)  1 1/16 (6.25%)  2 2/14 (14.29%)  2 0/15 (0.00%)  0 1/15 (6.67%)  1
Tooth infection *  1/15 (6.67%)  1 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Upper respiratory tract infection *  2/15 (13.33%)  2 4/16 (25.00%)  9 4/14 (28.57%)  6 3/15 (20.00%)  4 1/15 (6.67%)  1
Urinary tract infection *  1/15 (6.67%)  1 1/16 (6.25%)  1 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Viral infection *  1/15 (6.67%)  1 0/16 (0.00%)  0 0/14 (0.00%)  0 1/15 (6.67%)  1 1/15 (6.67%)  1
Injury, poisoning and procedural complications           
Contusion *  0/15 (0.00%)  0 0/16 (0.00%)  0 3/14 (21.43%)  3 0/15 (0.00%)  0 1/15 (6.67%)  1
Injury *  0/15 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 1/15 (6.67%)  1
Joint dislocation *  1/15 (6.67%)  1 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Ligament sprain *  1/15 (6.67%)  1 0/16 (0.00%)  0 0/14 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0
Muscle strain *  1/15 (6.67%)  2 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Stress fracture *  1/15 (6.67%)  1 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Investigations           
Arthroscopy *  0/15 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0
Neutrophil count decreased *  0/15 (0.00%)  0 1/16 (6.25%)  1 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Musculoskeletal and connective tissue disorders           
Arthralgia *  1/15 (6.67%)  1 0/16 (0.00%)  0 0/14 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0
Back pain *  0/15 (0.00%)  0 1/16 (6.25%)  1 0/14 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0
Musculoskeletal pain *  0/15 (0.00%)  0 0/16 (0.00%)  0 1/14 (7.14%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0
Myalgia *  0/15 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0
Pain in extremity *  1/15 (6.67%)  1 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Nervous system disorders           
Dizziness *  1/15 (6.67%)  1 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Dysgeusia *  1/15 (6.67%)  1 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Headache *  3/15 (20.00%)  3 3/16 (18.75%)  3 4/14 (28.57%)  7 1/15 (6.67%)  1 1/15 (6.67%)  1
Hypoaesthesia *  0/15 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 1/15 (6.67%)  1
Migraine *  1/15 (6.67%)  3 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Myoclonus *  0/15 (0.00%)  0 0/16 (0.00%)  0 1/14 (7.14%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0
Sinus headache *  0/15 (0.00%)  0 1/16 (6.25%)  1 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Syncope *  0/15 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 1/15 (6.67%)  1
Psychiatric disorders           
Depression *  0/15 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0
Reproductive system and breast disorders           
Breast pain *  0/15 (0.00%)  0 1/16 (6.25%)  1 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Respiratory, thoracic and mediastinal disorders           
Cough *  2/15 (13.33%)  2 1/16 (6.25%)  1 1/14 (7.14%)  1 2/15 (13.33%)  4 0/15 (0.00%)  0
Dyspnoea *  0/15 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0
Epistaxis *  0/15 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 1/15 (6.67%)  1
Nasal congestion *  0/15 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 1/15 (6.67%)  1 1/15 (6.67%)  1
Oropharyngeal pain *  0/15 (0.00%)  0 0/16 (0.00%)  0 1/14 (7.14%)  3 0/15 (0.00%)  0 2/15 (13.33%)  2
Respiratory tract congestion *  0/15 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0
Rhinitis allergic *  0/15 (0.00%)  0 1/16 (6.25%)  1 0/14 (0.00%)  0 1/15 (6.67%)  1 1/15 (6.67%)  1
Rhinorrhoea *  0/15 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 1/15 (6.67%)  1
Sinus congestion *  0/15 (0.00%)  0 0/16 (0.00%)  0 1/14 (7.14%)  1 0/15 (0.00%)  0 2/15 (13.33%)  2
Throat irritation *  0/15 (0.00%)  0 0/16 (0.00%)  0 1/14 (7.14%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0
Skin and subcutaneous tissue disorders           
Acne *  0/15 (0.00%)  0 2/16 (12.50%)  2 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Dermal cyst *  0/15 (0.00%)  0 0/16 (0.00%)  0 1/14 (7.14%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0
Ingrowing nail *  0/15 (0.00%)  0 0/16 (0.00%)  0 1/14 (7.14%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0
Lipodystrophy acquired *  0/15 (0.00%)  0 1/16 (6.25%)  1 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Lipohypertrophy *  0/15 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0
Rash *  0/15 (0.00%)  0 0/16 (0.00%)  0 1/14 (7.14%)  1 1/15 (6.67%)  1 0/15 (0.00%)  0
Rash generalised *  0/15 (0.00%)  0 0/16 (0.00%)  0 1/14 (7.14%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0
Skin irritation *  1/15 (6.67%)  1 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Swelling face *  0/15 (0.00%)  0 1/16 (6.25%)  1 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Surgical and medical procedures           
Tooth extraction *  1/15 (6.67%)  1 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0
Wisdom teeth removal *  0/15 (0.00%)  0 0/16 (0.00%)  0 0/14 (0.00%)  0 0/15 (0.00%)  0 1/15 (6.67%)  1
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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: Kimberly Steinmann, MD
Organization: Grifols Therapeutics LLC
Phone: 919-308-5444
Responsible Party: Grifols Therapeutics LLC
ClinicalTrials.gov Identifier: NCT02093221     History of Changes
Other Study ID Numbers: GTI1302
First Submitted: March 11, 2014
First Posted: March 20, 2014
Results First Submitted: March 23, 2018
Results First Posted: April 19, 2018
Last Update Posted: September 5, 2018