Safety/Tolerability/Pharmacokinetic (PK)/Pharmacodynamics (PD) Study of BMN701 in Patients With Late-Onset Pompe Disease
Sponsor
BioMarin Pharmaceutical (Industry)
Overall Status
Completed
CT.gov ID
NCT01230801
Collaborator
(none)
22
10
1
25.6
2.2
0.1
Study Details
Study Description
Brief Summary
A Phase 1/2, open-label, multicenter, multiple dose escalation study of BMN 701 administered by intravenous infusion every 2 weeks over a 24-week treatment period to patients with late-onset Pompe disease.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
22 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2 Open-label Study of the Safety, Tolerability, Pharmacokinetics, Pharmacodynamic and Preliminary Efficacy of BMN 701 (GILT-tagged Recombinant Human GAA) in Patients With Late-onset Pompe Disease
Actual Study Start Date
:
Jan 17, 2011
Actual Primary Completion Date
:
Mar 6, 2013
Actual Study Completion Date
:
Mar 6, 2013
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: BMN 701 IV infusion |
Biological: BMN 701
GILT-tagged recombinant human GAA
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Adverse Events [24 weeks]
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Secondary Outcome Measures
- Change From Baseline in Six Minutes Walk Test [Baseline up to 24 weeks]
Change from Baseline in Six Minutes Walk Test. The 6MWT measured the maximum distance the subject could walk on a flat, hard surface in a period of 6 minutes
Other Outcome Measures
- Change From Baseline in Percent Predicted Upright Forced Vital Capacity [Baseline up to 24 week]
Change from Baseline in Percent Predicted Upright Forced Vital Capacity. Changes in respiratory function were assessed by measurement of MEP, MIP and MVV; and percent predicted upright and supine FVC.
- Change From Baseline in Percent Predicted Supine Forced Vital Capacity [Baseline up to 24 weeks]
Change from Baseline in Percent Predicted Supine Forced Vital Capacity. Changes in respiratory function were assessed by measurement of MEP, MIP and MVV; and percent predicted upright and supine FVC.
- Change From Baseline in Percent Predicted Upright Maximum Expiratory Pressure [Baseline up to 24 weeks]
Change from Baseline in Percent Predicted Upright Maximum Expiratory Pressure. Changes in respiratory function were assessed by measurement of MEP, MIP and MVV; and percent predicted upright and supine FVC.
- Change From Baseline in Percent Predicted Upright Maximum Inspiratory Pressure [Baseline up to 24 weeks]
Change from Baseline in Percent Predicted Upright Maximum Inspiratory Pressure. Changes in respiratory function were assessed by measurement of MEP, MIP and MVV; and percent predicted upright and supine FVC.
- Change From Baseline in Upright Maximum Ventilatory Volume [Baseline up to 24 weeks]
Change from Baseline in Upright Maximum Ventilatory Volume. Changes in respiratory function were assessed by measurement of MEP, MIP and MVV; and percent predicted upright and supine FVC.
Eligibility Criteria
Criteria
Ages Eligible for Study:
13 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion criteria:
-
Patient has been diagnosed with Pompe Disease prior to or during the screening period based on 2 GAA gene mutations and either: endogenous GAA activity <75% of the lower limit of the normal adult range reported by the testing laboratory, as assessed in cultured skin fibroblasts -or- endogenous GAA activity <75% of the lower limit of the normal adult range reported by the testing laboratory, as assessed by dried blood spot or whole blood assay;
-
Patient is male or female and 13 years of age or older at the time of enrollment in the study;
-
Sexually active patients must be willing to use an acceptable method of contraception while participating in the study and for at least 4 months following the last dose of BMN 701;
-
If patient is female and not considered to be of childbearing potential, she is at least 2 years post-menopausal or had tubal ligation at least 1 year prior to screening, or who have had total hysterectomy;
-
If patient is female and of childbearing potential, she has negative urine pregnancy tests during the Screening Period and at the Baseline visit and be willing to have additional pregnancy tests during the study;
-
Patient has ≥30% predicted upright FVC and either <80% predicted upright FVC, or >10% reduction in supine FVC compared to upright FVC during the Screening Period;
-
Patient is naïve to Enzyme Replacement Therapy (ERT) with rhGAA;
-
Patient must be able to ambulate at least 40 meters (131.2 feet) on the 6MWT conducted at the Screening visit (use of assistive devices such as walker, cane, or crutches, is permitted); and
-
If subject was female, she was not lactating
Exclusion criteria:
-
Patient has a history of diabetes or other disease known to cause hypoglycemia and is currently receiving, or might anticipate receiving, hypoglycemic agents during the course of the study;
-
Patient has been on any immunosuppressive medication other than glucocorticosteroids within 1 year prior to enrollment into this study;
-
Patient requires invasive ventilatory assistance at the time of enrollment into the study;
-
Patient has received any investigational medication within 30 days prior to the first dose of study drug or is scheduled to receive any investigational drug other than BMN 701 during the course of the study;
-
Patient has previously been admitted to the study;
-
Patient is breastfeeding at screening or planning to become pregnant (self or partner) at any time during the study;
-
Patient has a medical condition or extenuating circumstance that, in the opinion of the Investigator, might compromise the patient's ability to comply with the protocol requirements or compromise the patient's well being or safety;
-
Patient has any condition that, in the view of the Investigator, places the patient at high risk of poor treatment compliance or of not completing the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Univ of California San Diego School of Medicine | La Jolla | California | United States | 92103-8765 |
| 2 | University of Florida College of Medicine | Gainesville | Florida | United States | 32610 |
| 3 | University of Kansas Medical Center | Kansas City | Kansas | United States | 66160 |
| 4 | Royal Adelaide Hospital, SA Pathology | Adelaide | Adelaide, SA | Australia | 5006 |
| 5 | Hôpital de I´Archet- Centre Hospitalier Universitaire Nice | Nice | France | 06202 | |
| 6 | Hôpital Pitié-Salpêtrière | Paris Cedex 13 | France | 75651 | |
| 7 | Zentrum für Kinder- und Jugenmedizin | Mainz | Rheinland-pfalz | Germany | 55131 |
| 8 | Old Queen Elizabeth Hospital, Department of Medicine | Birmingham | United Kingdom | B15 2TH | |
| 9 | Royal Free Hospital | London | United Kingdom | NW3 2QG | |
| 10 | Salford Royal Hospital NHS Trust | Salford | United Kingdom | M6 8HD |
Sponsors and Collaborators
- BioMarin Pharmaceutical
Investigators
- Study Director: Medical Monitor, BioMarin Pharmaceutical
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
BioMarin Pharmaceutical
ClinicalTrials.gov Identifier:
NCT01230801
Other Study ID Numbers:
- POM-001
- 2010-023561-22
First Posted:
Oct 29, 2010
Last Update Posted:
Jun 11, 2018
Last Verified:
May 1, 2018
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | BMN 701 5 mg/kg | BMN 701 10 mg/kg | BMN 701 20 mg/kg |
|---|---|---|---|
| Arm/Group Description | BMN 701 5 mg/kg IV | BMN 701 10 mg/kg IV | BMN 701 20 mg/kg IV |
| Period Title: Overall Study | |||
| STARTED | 3 | 3 | 16 |
| COMPLETED | 3 | 3 | 15 |
| NOT COMPLETED | 0 | 0 | 1 |
Baseline Characteristics
| Arm/Group Title | BMN 701 5 mg/kg | BMN 701 10 mg/kg | BMN 701 20 mg/kg | Total |
|---|---|---|---|---|
| Arm/Group Description | BMN 701 5 mg/kg IV | BMN 701 10 mg/kg IV | BMN 701 20 mg/kg IV | Total of all reporting groups |
| Overall Participants | 3 | 3 | 16 | 22 |
| Age (Count of Participants) | ||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
3
100%
|
3
100%
|
16
100%
|
22
100%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
51.7
(6.81)
|
42.3
(12.90)
|
50.1
(5.37)
|
49.3
(7.00)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
0
0%
|
2
66.7%
|
6
37.5%
|
8
36.4%
|
| Male |
3
100%
|
1
33.3%
|
10
62.5%
|
14
63.6%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||
| Hispanic or Latino |
0
0%
|
1
33.3%
|
0
0%
|
1
4.5%
|
| Not Hispanic or Latino |
3
100%
|
2
66.7%
|
16
100%
|
21
95.5%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race/Ethnicity, Customized (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| White |
3
100%
|
3
100%
|
15
93.8%
|
21
95.5%
|
| Other |
0
0%
|
0
0%
|
1
6.3%
|
1
4.5%
|
| Region of Enrollment (Count of Participants) | ||||
| Australia |
0
0%
|
0
0%
|
4
25%
|
4
18.2%
|
| France |
0
0%
|
0
0%
|
2
12.5%
|
2
9.1%
|
| Germany |
0
0%
|
0
0%
|
1
6.3%
|
1
4.5%
|
| United Kingdom |
0
0%
|
0
0%
|
6
37.5%
|
6
27.3%
|
| United States |
3
100%
|
3
100%
|
3
18.8%
|
9
40.9%
|
Outcome Measures
| Title | Number of Participants With Adverse Events |
|---|---|
| Description | Number of Participants with Adverse Events as a Measure of Safety and Tolerability |
| Time Frame | 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population |
| Arm/Group Title | BMN 701 5 mg/kg | BMN 701 10 mg/kg | BMN 701 20 mg/kg |
|---|---|---|---|
| Arm/Group Description | BMN 701 5 mg/kg IV | BMN 701 10 mg/kg IV | BMN 701 20 mg/kg IV |
| Measure Participants | 3 | 3 | 16 |
| Count of Participants [Participants] |
3
100%
|
3
100%
|
15
93.8%
|
| Title | Change From Baseline in Six Minutes Walk Test |
|---|---|
| Description | Change from Baseline in Six Minutes Walk Test. The 6MWT measured the maximum distance the subject could walk on a flat, hard surface in a period of 6 minutes |
| Time Frame | Baseline up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population. As some patients did not attend or all tests were not completed at each visit, some time points had different numbers of patients analyzed. The total number of patients analyzed for each arm is listed as the maximum patients analyzed at any given time point. |
| Arm/Group Title | BMN 701 5 mg/kg | BMN 701 10 mg/kg | BMN 701 20 mg/kg | Total |
|---|---|---|---|---|
| Arm/Group Description | BMN 701 5 mg/kg IV | BMN 701 10 mg/kg IV | BMN 701 20 mg/kg IV | Total Results |
| Measure Participants | 3 | 3 | 16 | 22 |
| Baseline |
334
(227.12)
|
360
(51.4)
|
354.5
(156.94)
|
352.5
(151.05)
|
| Change from Baseline - Week 6 |
-2.5
(23.33)
|
-30.3
(56.50)
|
19.8
(35.11)
|
10.5
(40.08)
|
| Change from Baseline - Week 12 |
31.2
(78.81)
|
-13.7
(8.04)
|
11.1
(42.67)
|
10.4
(45.32)
|
| Change from Baseline - Week 18 |
43.3
(89.44)
|
-79.0
(104.61)
|
16.4
(55.09)
|
6.6
(73.43)
|
| Change from Baseline - Week 24 |
36.0
(76.02)
|
-42.7
(12.57)
|
22.3
(54.23)
|
15.3
(56.97)
|
| Title | Change From Baseline in Percent Predicted Upright Forced Vital Capacity |
|---|---|
| Description | Change from Baseline in Percent Predicted Upright Forced Vital Capacity. Changes in respiratory function were assessed by measurement of MEP, MIP and MVV; and percent predicted upright and supine FVC. |
| Time Frame | Baseline up to 24 week |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population. As some patients did not attend or all tests were not completed at each visit, some time points had different numbers of patients analyzed. The total number of patients analyzed for each arm is listed as the maximum patients analyzed at any given time point. |
| Arm/Group Title | BMN 701 5 mg/kg | BMN 701 10 mg/kg | BMN 701 20 mg/kg | Total |
|---|---|---|---|---|
| Arm/Group Description | BMN 701 5 mg/kg IV | BMN 701 10 mg/kg IV | BMN 701 20 mg/kg IV | Total Results |
| Measure Participants | 3 | 3 | 16 | 22 |
| Baseline |
69.3
(19.73)
|
67.3
(26.58)
|
58.1
(18.42)
|
60.9
(19.21)
|
| Change from Baseline - Week 6 |
4.0
(4.24)
|
-2.0
(2.65)
|
0.4
(3.3)
|
0.4
(3.46)
|
| Change from Baseline - Week 12 |
-2.6
(9.5)
|
-3.7
(2.89)
|
1.6
(4.35)
|
0.3
(5.25)
|
| Change from Baseline - Week 18 |
1.5
(4.09)
|
0.3
(3.06)
|
1.2
(4.49)
|
1.1
(4.1)
|
| Change from Baseline - Week 24 |
1.0
(2.65)
|
-1.7
(3.06)
|
1.2
(3.89)
|
0.8
(3.65)
|
| Title | Change From Baseline in Percent Predicted Supine Forced Vital Capacity |
|---|---|
| Description | Change from Baseline in Percent Predicted Supine Forced Vital Capacity. Changes in respiratory function were assessed by measurement of MEP, MIP and MVV; and percent predicted upright and supine FVC. |
| Time Frame | Baseline up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population. As some patients did not attend or all tests were not completed at each visit, some time points had different numbers of patients analyzed. The total number of patients analyzed for each arm is listed as the maximum patients analyzed at any given time point. |
| Arm/Group Title | BMN 701 5 mg/kg | BMN 701 10 mg/kg | BMN 701 20 mg/kg | Total |
|---|---|---|---|---|
| Arm/Group Description | BMN 701 5 mg/kg IV | BMN 701 10 mg/kg IV | BMN 701 20 mg/kg IV | Total Results |
| Measure Participants | 3 | 3 | 16 | 22 |
| Baseline |
36.7
(17.95)
|
47.7
(32.58)
|
46.3
(21.93)
|
45
(22.1)
|
| Change from Baseline - Week 6 |
2.1
(1.2)
|
-1.3
(4.04)
|
-0.8
(4.86)
|
-0.6
(4.44)
|
| Change from Baseline - Week 12 |
0.3
(4.22)
|
-4.7
(2.89)
|
3.3
(3.87)
|
1.5
(4.7)
|
| Change from Baseline - Week 18 |
1.3
(1.53)
|
-1.3
(6.66)
|
2.3
(3.14)
|
1.5
(3.7)
|
| Change from Baseline - Week 24 |
2.0
(3.0)
|
-3.3
(5.51)
|
1.1
(4.42)
|
0.5
(4.53)
|
| Title | Change From Baseline in Percent Predicted Upright Maximum Expiratory Pressure |
|---|---|
| Description | Change from Baseline in Percent Predicted Upright Maximum Expiratory Pressure. Changes in respiratory function were assessed by measurement of MEP, MIP and MVV; and percent predicted upright and supine FVC. |
| Time Frame | Baseline up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population. As some patients did not attend or all tests were not completed at each visit, some time points had different numbers of patients analyzed. The total number of patients analyzed for each arm is listed as the maximum patients analyzed at any given time point. No patient had baseline assessment in group of BMN 701 5 mg/kg. |
| Arm/Group Title | BMN 701 5 mg/kg | BMN 701 10 mg/kg | BMN 701 20 mg/kg | Total |
|---|---|---|---|---|
| Arm/Group Description | BMN 701 5 mg/kg IV | BMN 701 10 mg/kg IV | BMN 701 20 mg/kg IV | Total IV |
| Measure Participants | 0 | 3 | 16 | 22 |
| Baseline |
31.1
(6.64)
|
36.3
(15.46)
|
35.5
(14.42)
|
|
| Change from Baseline - Week 6 |
6.8
(4.06)
|
3.2
(5.38)
|
3.8
(5.27)
|
|
| Change from Baseline - Week 12 |
1.4
(4.53)
|
2.2
(8.68)
|
2.0
(8.07)
|
|
| Change from Baseline - Week 18 |
1.2
(2.06)
|
6.9
(7.21)
|
6.0
(6.94)
|
|
| Change from Baseline - Week 24 |
2.5
(10.4)
|
5.2
(8.25)
|
4.8
(8.36)
|
| Title | Change From Baseline in Percent Predicted Upright Maximum Inspiratory Pressure |
|---|---|
| Description | Change from Baseline in Percent Predicted Upright Maximum Inspiratory Pressure. Changes in respiratory function were assessed by measurement of MEP, MIP and MVV; and percent predicted upright and supine FVC. |
| Time Frame | Baseline up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population. As some patients did not attend or all tests were not completed at each visit, some time points had different numbers of patients analyzed. The total number of patients analyzed for each arm is listed as the maximum patients analyzed at any given time point. No patient had baseline assessment in group of BMN 701 5 mg/kg. |
| Arm/Group Title | BMN 701 5 mg/kg | BMN 701 10 mg/kg | BMN 701 20 mg/kg | Total |
|---|---|---|---|---|
| Arm/Group Description | BMN 701 5 mg/kg IV | BMN 701 10 mg/kg IV | BMN 701 20 mg/kg IV | Total Results |
| Measure Participants | 0 | 3 | 16 | 22 |
| Baseline |
39.5
(21.87)
|
40.5
(25.01)
|
40.3
(23.97)
|
|
| Change from baseline at week 6 |
1.7
(1.46)
|
5.3
(9.8)
|
4.7
(9.06)
|
|
| Change from baseline at week 12 |
3.4
(6.74)
|
11.4
(10.92)
|
10.1
(10.65)
|
|
| Change from baseline at week 18 |
2.9
(11.77)
|
14.5
(14.48)
|
12.6
(14.45)
|
|
| Change from baseline at week 24 |
0.7
(6.69)
|
11.1
(8.31)
|
9.5
(8.81)
|
| Title | Change From Baseline in Upright Maximum Ventilatory Volume |
|---|---|
| Description | Change from Baseline in Upright Maximum Ventilatory Volume. Changes in respiratory function were assessed by measurement of MEP, MIP and MVV; and percent predicted upright and supine FVC. |
| Time Frame | Baseline up to 24 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT Population. As some patients did not attend or all tests were not completed at each visit, some time points had different numbers of patients analyzed. The total number of patients analyzed for each arm is listed as the maximum patients analyzed at any given time point. No patient had baseline assessment in group of BMN 701 5 mg/kg. |
| Arm/Group Title | BMN 701 5 mg/kg | BMN 701 10 mg/kg | BMN 701 20 mg/kg | Total |
|---|---|---|---|---|
| Arm/Group Description | BMN 701 5 mg/kg IV | BMN 701 10 mg/kg IV | BMN 701 20 mg/kg IV | Total Results |
| Measure Participants | 0 | 3 | 16 | 22 |
| Baseline |
76
(41.04)
|
67.6
(25.9)
|
68.9
(27.5)
|
|
| Change from Baseline - Week 6 |
-1.0
(0.35)
|
1.5
(11.1)
|
1.1
(10.18)
|
|
| Change from Baseline - Week 12 |
-1.1
(2.73)
|
3.8
(11.64)
|
3.0
(10.82)
|
|
| Change from Baseline - Week 18 |
-3.9
(2.86)
|
4.7
(10.89)
|
3.3
(10.46)
|
|
| Change from Baseline - Week 24 |
-0.7
(9.1)
|
2.3
(10.71)
|
1.8
(10.28)
|
Adverse Events
| Time Frame | 32 weeks (27 days of screening and baseline measurements + 24 weeks of treatment + 20 days of follow-up) | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | BMN 701 5 mg/kg | BMN 701 10 mg/kg | BMN 701 20 mg/kg | Total | ||||
| Arm/Group Description | BMN 701 5 mg/kg IV | BMN 701 10 mg/kg IV | BMN 701 20 mg/kg IV | Total Results | ||||
All Cause Mortality |
||||||||
| BMN 701 5 mg/kg | BMN 701 10 mg/kg | BMN 701 20 mg/kg | Total | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 0/3 (0%) | 0/16 (0%) | 0/22 (0%) | ||||
Serious Adverse Events |
||||||||
| BMN 701 5 mg/kg | BMN 701 10 mg/kg | BMN 701 20 mg/kg | Total | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 0/3 (0%) | 4/16 (25%) | 4/22 (18.2%) | ||||
| Immune system disorders | ||||||||
| Hypersensitivity | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Metabolism and nutrition disorders | ||||||||
| Hypoglycaemia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Psychiatric disorders | ||||||||
| Aggression | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Vascular disorders | ||||||||
| Hypertensive crisis | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||||
| BMN 701 5 mg/kg | BMN 701 10 mg/kg | BMN 701 20 mg/kg | Total | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/3 (100%) | 3/3 (100%) | 15/16 (93.8%) | 21/22 (95.5%) | ||||
| Cardiac disorders | ||||||||
| Bradycardia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Bundle branch block right | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Palpitations | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 3/16 (18.8%) | 4 | 4/22 (18.2%) | 5 |
| Sinus tachycardia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Tachycardia | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 4/16 (25%) | 16 | 5/22 (22.7%) | 18 |
| Eye disorders | ||||||||
| Diplopia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Vision blurred | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Gastrointestinal disorders | ||||||||
| Abdominal discomfort | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/16 (12.5%) | 2 | 2/22 (9.1%) | 2 |
| Abdominal distension | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Abdominal pain | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 2 | 1/22 (4.5%) | 2 |
| Abdominal pain upper | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/16 (12.5%) | 2 | 2/22 (9.1%) | 2 |
| Abdominal tenderness | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Constipation | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/16 (12.5%) | 2 | 2/22 (9.1%) | 2 |
| Diarrhoea | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 4/16 (25%) | 5 | 5/22 (22.7%) | 6 |
| Dry mouth | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Dyspepsia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Dysphagia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Epigastric discomfort | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Gastritis | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Gastrooesophageal reflux disease | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Haemorrhoids | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Nausea | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 8/16 (50%) | 15 | 8/22 (36.4%) | 15 |
| Rectal haemorrhage | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Retching | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/16 (0%) | 0 | 1/22 (4.5%) | 1 |
| Tongue discolouration | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Vomiting | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 5/16 (31.3%) | 9 | 7/22 (31.8%) | 11 |
| General disorders | ||||||||
| Application site erythema | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Asthenia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Chest discomfort | 1/3 (33.3%) | 6 | 1/3 (33.3%) | 2 | 5/16 (31.3%) | 6 | 7/22 (31.8%) | 14 |
| Chills | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 3/16 (18.8%) | 3 | 4/22 (18.2%) | 4 |
| Fatigue | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 0/16 (0%) | 0 | 2/22 (9.1%) | 2 |
| Feeling cold | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/16 (6.3%) | 1 | 2/22 (9.1%) | 2 |
| Feeling hot | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 3/16 (18.8%) | 3 | 3/22 (13.6%) | 3 |
| Infusion site discomfort | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Local swelling | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 2 | 1/22 (4.5%) | 2 |
| Malaise | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/16 (12.5%) | 3 | 2/22 (9.1%) | 3 |
| Non-cardiac chest pain | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Oedema peripheral | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 3/16 (18.8%) | 3 | 3/22 (13.6%) | 3 |
| Pain | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/16 (6.3%) | 1 | 2/22 (9.1%) | 2 |
| Pyrexia | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/16 (0%) | 0 | 1/22 (4.5%) | 1 |
| Tenderness | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Thirst | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Vaccination site inflammation | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Vessel puncture site bruise | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Infections and infestations | ||||||||
| Candida infection | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Laryngitis | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/16 (0%) | 0 | 1/22 (4.5%) | 1 |
| Localised infection | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Lower respiratory tract infection | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/16 (12.5%) | 2 | 2/22 (9.1%) | 2 |
| Nasopharyngitis | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 2/16 (12.5%) | 3 | 3/22 (13.6%) | 5 |
| Sinusitis | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/16 (0%) | 0 | 1/22 (4.5%) | 1 |
| Tooth abscess | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Upper respiratory tract infection | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/16 (12.5%) | 2 | 2/22 (9.1%) | 2 |
| Urinary tract infection | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Injury, poisoning and procedural complications | ||||||||
| Animal bite | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Arthropod bite | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Contusion | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 3/16 (18.8%) | 4 | 5/22 (22.7%) | 6 |
| Fall | 1/3 (33.3%) | 2 | 3/3 (100%) | 5 | 3/16 (18.8%) | 4 | 7/22 (31.8%) | 11 |
| Infusion related reaction | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/16 (12.5%) | 2 | 2/22 (9.1%) | 2 |
| Laceration | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Post procedural haemorrhage | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Procedural pain | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Investigations | ||||||||
| Blood glucose decreased | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Body temperature increased | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/16 (0%) | 0 | 1/22 (4.5%) | 1 |
| Cardiac murmur | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Complement factor decreased | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Respiratory rate increased | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 5 | 1/22 (4.5%) | 5 |
| Metabolism and nutrition disorders | ||||||||
| Dehydration | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Hyperglycaemia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Hyperphagia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Hypoglycaemia | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 14/16 (87.5%) | 41 | 14/22 (63.6%) | 41 |
| Lactic acidosis | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/16 (6.3%) | 1 | 2/22 (9.1%) | 2 |
| Back pain | 2/3 (66.7%) | 4 | 0/3 (0%) | 0 | 2/16 (12.5%) | 3 | 4/22 (18.2%) | 7 |
| Joint swelling | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Muscle spasms | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Neck pain | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 2/22 (9.1%) | 3 |
| Pain in extremity | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 3/16 (18.8%) | 4 | 3/22 (13.6%) | 4 |
| Nervous system disorders | ||||||||
| Disturbance in attention | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Dizziness | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 6/16 (37.5%) | 9 | 7/22 (31.8%) | 10 |
| Headache | 1/3 (33.3%) | 2 | 2/3 (66.7%) | 8 | 6/16 (37.5%) | 27 | 9/22 (40.9%) | 37 |
| Hypoaesthesia | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/16 (0%) | 0 | 1/22 (4.5%) | 1 |
| Lethargy | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Paraesthesia | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 2/22 (9.1%) | 2 |
| Tremor | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 3/16 (18.8%) | 4 | 3/22 (13.6%) | 4 |
| Psychiatric disorders | ||||||||
| Anxiety | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/16 (0%) | 0 | 1/22 (4.5%) | 1 |
| Confusional state | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Depression | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Depressive symptom | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Nervousness | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/16 (12.5%) | 2 | 2/22 (9.1%) | 2 |
| Renal and urinary disorders | ||||||||
| Haematuria | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Reproductive system and breast disorders | ||||||||
| Dysmenorrhoea | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/16 (0%) | 0 | 1/22 (4.5%) | 1 |
| Vaginal haemorrhage | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 2/16 (12.5%) | 2 | 4/22 (18.2%) | 4 |
| Dyspnoea | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 5/16 (31.3%) | 10 | 6/22 (27.3%) | 12 |
| Dyspnoea exertional | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/16 (0%) | 0 | 1/22 (4.5%) | 1 |
| Hypopnoea | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Laryngeal oedema | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Nasal congestion | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 2/22 (9.1%) | 2 |
| Oropharyngeal pain | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 3/16 (18.8%) | 3 | 4/22 (18.2%) | 4 |
| Pharyngeal oedema | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Respiratory distress | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Rhinorrhoea | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Throat irritation | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/16 (0%) | 0 | 1/22 (4.5%) | 1 |
| Skin and subcutaneous tissue disorders | ||||||||
| Cold sweat | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 2 | 1/22 (4.5%) | 2 |
| Dermatitis allergic | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Eczema | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/16 (12.5%) | 2 | 2/22 (9.1%) | 2 |
| Hyperhidrosis | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 2 | 1/22 (4.5%) | 2 |
| Pruritus | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/16 (12.5%) | 4 | 2/22 (9.1%) | 4 |
| Rash | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 4/16 (25%) | 5 | 4/22 (18.2%) | 5 |
| Rash erythematous | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Rash maculo-papular | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Rash pruritic | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/16 (6.3%) | 4 | 2/22 (9.1%) | 5 |
| Skin discolouration | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Urticaria | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/16 (6.3%) | 13 | 2/22 (9.1%) | 14 |
| Vascular disorders | ||||||||
| Flushing | 1/3 (33.3%) | 5 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 2/22 (9.1%) | 6 |
| Haematoma | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/16 (0%) | 0 | 1/22 (4.5%) | 1 |
| Hot flush | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Hypertension | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 3/16 (18.8%) | 5 | 3/22 (13.6%) | 5 |
| Hypotension | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Pallor | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/16 (12.5%) | 2 | 2/22 (9.1%) | 2 |
| Poor venous access | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/16 (0%) | 0 | 1/22 (4.5%) | 1 |
| Systolic hypertension | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
| Venous thrombosis | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/16 (6.3%) | 1 | 1/22 (4.5%) | 1 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Manager, Clinical Operations |
|---|---|
| Organization | BioMarin Pharmaceutical Inc. |
| Phone | 415-455-7448 |
| Slava.Titov@bmrn.com |
Responsible Party:
BioMarin Pharmaceutical
ClinicalTrials.gov Identifier:
NCT01230801
Other Study ID Numbers:
- POM-001
- 2010-023561-22
First Posted:
Oct 29, 2010
Last Update Posted:
Jun 11, 2018
Last Verified:
May 1, 2018