Dose-Finding Study to Evaluate the Safety, Efficacy, & Tolerability of Multiple Doses of rAvPAL-PEG in Subjects With PKU
Sponsor
BioMarin Pharmaceutical (Industry)
Overall Status
Completed
CT.gov ID
NCT00925054
Collaborator
(none)
40
11
5
69
3.6
0.1
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate whether weekly injections of phenylalanine ammonia lyase (rAvPAL-PEG) can reduce blood phenylalanine concentrations in PKU subjects and whether repeated administration is safe.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
This is a 2 part, Phase 2, open-label dose-finding study in approximately 35 subjects with PKU. Seven dose cohorts are planned, each consisting of 5 subjects. In Part 1, the planned starting dose levels are those tested in PAL 001 (0.001, 0.003, 0.01, 0.03, 0.1, 0.3, and 1.0 mg/kg), provided no dose limiting toxicity was observed in PAL 001. In Parts 1 and 2, study drug will be administered by clinic staff.
Subjects who completed participation in PAL 001 will receive priority to participate in PAL 002. rAvPAL PEG naïve subjects will be enrolled to fill any dose cohort vacancies resulting from subjects who did not complete PAL 001 or who chose not to continue into PAL 002. In addition, if the number of dose cohorts determined in PAL 001 is less than 7, additional naïve subjects may be added to the existing dose cohorts to provide a total of approximately 35 subjects entering Part 1 of PAL 002. Furthermore, if serial dosing of cohorts in Part 1 of PAL 002 is stopped, additional subjects (either naïve subjects or PAL 001 subjects) may be added to the existing cohorts so that total study enrollment is approximately 35 subjects. In any of these cases, additional subjects will be enrolled sequentially from lowest to highest dose cohort.
Diet will not be altered during the course of this study, except as necessary for safety.
Subjects will be evaluated for safety and for blood Phe concentrations throughout the study. Toxicity will be measured according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 3.
A Data Monitoring Committee will monitor the study.
Study Design
Study Type:
Interventional
Actual Enrollment
:
40 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 2, Open-Label Dose-Finding Study to Evaluate the Safety, Efficacy, and Tolerability of Multiple Subcutaneous (SC) Doses of rAvPAL-PEG in Subjects With PKU
Study Start Date
:
Sep 1, 2009
Actual Primary Completion Date
:
Jun 1, 2015
Actual Study Completion Date
:
Jun 1, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: rAvPAL-PEG 0.001 mg/kg Subjects will start on rAvPAL-PEG 0.001 mg/kg |
Drug: rAvPAL-PEG 0.001 mg/kg
In Part 1, the planned starting dose levels is 0.001 mg/kg
|
| Experimental: rAvPAL-PEG 0.003 mg/kg Subjects will start on rAvPAL-PEG 0.003 mg/kg |
Drug: rAvPAL-PEG 0.003 mg/kg
In Part 1, the planned starting dose levels is 0.003 mg/kg
|
| Experimental: rAvPAL-PEG 0.01 mg/kg Subjects will start on rAvPAL-PEG 0.01 mg/kg |
Drug: rAvPAL-PEG 0.01 mg/kg
In Part 1, the planned starting dose levels is 0.01 mg/kg
|
| Experimental: rAvPAL-PEG 0.03 mg/kg Subjects will start on rAvPAL-PEG 0.03 mg/kg |
Drug: rAvPAL-PEG 0.03 mg/kg
In Part 1, the planned starting dose levels is 0.03 mg/kg
|
| Experimental: rAvPAL-PEG 0.1 mg/kg Subjects will start on rAvPAL-PEG 0.1 mg/kg |
Drug: rAvPAL-PEG 0.1 mg/kg
In Part 1, the planned starting dose levels is 0.1 mg/kg
|
Outcome Measures
Primary Outcome Measures
- Blood Phenylalanine Concentrations [Baseline, Week 1/Day 5, Week 7, Week 16/Day 106]
Secondary Outcome Measures
- Study Drug Related Adverse Events [Screening, Weeks 1-22]
- Number of Participants With Positive PAL IgG Antibody [Baseline, Week 12]
Antibody against PAL (phenylalanine ammonia lyase) measured over time
- Number of Participants With Positive PAL IgM Antibody [Baseline, Week 12]
Antibody positivity over time
- Number of Participants With Positive PEG IgM Antibody [Baseline, Week 16]
Antibody positivity over time
- Number of Participants With Positive PEG IgG Antibody [Baseline, Week 16]
Antibody positivity over time
- Percentage of Participants With Positive Neutralizing Antibodies [NAb] [Baseline, Week 12]
Antibody positivity over time
- Percentage of Participants With Positive PAL IgE Antibody [Baselline, Week 12]
Antibody positivity over time
- Percentage of Participants With Positive Anti-PAL-PEG IgE Antibodies [Baseline, Week 12]
Antibody positivity over time
Other Outcome Measures
- Trough Concentration of BMN 165 [Baseline, Baseline/pre-dose, Week 7, and Week 16/Day 106]
Plasma concentrations of rAvPAL-PEG (BMN 165)
Eligibility Criteria
Criteria
Ages Eligible for Study:
16 Years
to 55 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
For subjects who did not participate in PAL-001, diagnosis of PKU with both of the following: Current blood Phe concentration of ≥ 600 mmol/L at Screening and average blood Phe concentration of ≥ 600 µmol/L over the past 3 years, using available data.
-
For subjects who did not participate in PAL-001, evidence that the subject is a non-responder to Kuvan® treatment (ie, 4 weeks of treatment with 20 mg/kg/day of Kuvan®, insufficient response per investigator determination, and treatment end date ≥ 14 days prior to Day 1 [ie, first dose]). Subjects who have had a previous response to Kuvan® treatment but are not currently taking Kuvan® because of noncompliance and have been off treatment for ≥ 6 months prior to Screening are eligible for participation.
-
Willing and able to provide written, signed informed consent, or, in the case of participants under the age of 18, provide written assent (if required) and written informed consent by a parent or legal guardian, after the nature of the study has been explained, and prior to any research-related procedures.
-
Between the ages of 16 and 55 years, inclusive.
-
Females of childbearing potential must have a negative pregnancy test at Screening and be willing to have additional pregnancy tests during the study. Females considered not of childbearing potential include those who have been in menopause at least 2 years, or had tubal ligation at least 1 year prior to Screening, or who have had total hysterectomy.
-
Sexually active subjects must be willing to use an acceptable method of contraception while participating in the study.
-
Maintained a stable diet with no significant modifications during the 4 weeks preceding the administration of study drug.
-
In generally good health as evidenced by physical examination, clinical laboratory evaluations (hematology, chemistry, and urinalysis), and electrocardiogram (ECG) at Screening.
-
Willing and able to comply with study procedures.
Exclusion Criteria:
-
Use of any investigational product (with the exception of rAvPAL-PEG) or investigational medical device within 30 days prior to Screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.
-
Use of any medication that is intended to treat PKU within 14 days prior to the administration of study drug.
-
Use or planned use of any injectable drugs containing PEG (other than rAvPAL-PEG), including Depo-Provera, within 3 months prior to Screening and during study participation.
-
A prior reaction that included systemic symptoms (eg, respiratory or gastrointestinal problems, hypotension, angioedema, anaphylaxis) to rAvPAL-PEG or a PEG containing product. Subjects with a prior systemic reaction of generalized rash may be eligible for participation per the discretion of the Principal Investigator in consultation with the Sponsor's Medical Officer.
-
Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) or to breastfeed at any time during the study.
-
Concurrent disease or condition that would interfere with study participation or safety (eg, history or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurological, oncologic, or psychiatric disease).
-
Any condition that, in the view of the PI, places the subject at high risk of poor treatment compliance or of not completing the study.
-
Alanine aminotransferase (ALT) concentration > 2 times the upper limit of normal.
-
Creatinine > 1.5 times the upper limit of normal.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The Children's Hospital | Aurora | Colorado | United States | 80045 |
| 2 | Emory Universty | Decatur | Georgia | United States | 30033 |
| 3 | Children's Memorial Hospital | Chicago | Illinois | United States | 60614 |
| 4 | University of Minnesota Medical Center-Fairview | Minneapolis | Minnesota | United States | 55455 |
| 5 | Washington University Center for Applied Research Sciences | Saint Louis | Missouri | United States | 63110 |
| 6 | Albany Medical Center | Albany | New York | United States | 12208 |
| 7 | Mount Sinai School of Medicine | New York | New York | United States | 10029 |
| 8 | Akron Children's Hospital | Akron | Ohio | United States | 44308 |
| 9 | Oregon Health & Science University | Portland | Oregon | United States | 97239 |
| 10 | University of Pittsburgh Medical Center | Pittsburgh | Pennsylvania | United States | 15213 |
| 11 | University of Utah Hospital | Salt Lake City | Utah | United States | 84132 |
Sponsors and Collaborators
- BioMarin Pharmaceutical
Investigators
- Study Director: Ari Gershman, MD, BioMarin Pharmaceutical
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
BioMarin Pharmaceutical
ClinicalTrials.gov Identifier:
NCT00925054
Other Study ID Numbers:
- PAL-002
First Posted:
Jun 19, 2009
Last Update Posted:
Feb 26, 2019
Last Verified:
Feb 1, 2019
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Keywords provided by BioMarin Pharmaceutical
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Starting Dose=0.001 mg/kg | Starting Dose=0.003 mg/kg | Starting Dose=0.01 mg/kg | Starting Dose=0.03 mg/kg | Starting Dose=0.1 mg/kg |
|---|---|---|---|---|---|
| Arm/Group Description | Subjects will start on rAvPAL-PEG 0.001 mg/kg | Subjects will start on rAvPAL-PEG 0.003 mg/kg | Subjects will start on rAvPAL-PEG 0.01 mg/kg | Subjects will start on rAvPAL-PEG 0.03 mg/kg | Subjects will start on rAvPAL-PEG 0.1 mg/kg |
| Period Title: Overall Study | |||||
| STARTED | 7 | 9 | 13 | 1 | 10 |
| COMPLETED | 7 | 8 | 12 | 0 | 10 |
| NOT COMPLETED | 0 | 1 | 1 | 1 | 0 |
Baseline Characteristics
| Arm/Group Title | Starting Dose=0.001 mg/kg | Starting Dose=0.003 mg/kg | Starting Dose=0.01 mg/kg | Starting Dose=0.03 mg/kg | Starting Dose=0.1 mg/kg | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects will start on rAvPAL-PEG 0.001 mg/kg | Subjects will start on rAvPAL-PEG 0.003 mg/kg | Subjects will start on rAvPAL-PEG 0.01 mg/kg | Subjects will start on rAvPAL-PEG 0.03 mg/kg | Subjects will start on rAvPAL-PEG 0.1 mg/kg | Total of all reporting groups |
| Overall Participants | 7 | 9 | 13 | 1 | 10 | 40 |
| Age (years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [years] |
23.3
(3.45)
|
29.2
(5.95)
|
26.5
(5.65)
|
22.0
|
25.2
(8.60)
|
26.1
(6.35)
|
| Age, Customized (Count of Participants) | ||||||
| < 18 years of age |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
20%
|
2
5%
|
| > or = 18 years of age |
7
100%
|
9
100%
|
13
100%
|
1
100%
|
8
80%
|
38
95%
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
3
42.9%
|
7
77.8%
|
6
46.2%
|
0
0%
|
4
40%
|
20
50%
|
| Male |
4
57.1%
|
2
22.2%
|
7
53.8%
|
1
100%
|
6
60%
|
20
50%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
10%
|
1
2.5%
|
| Not Hispanic or Latino |
7
100%
|
9
100%
|
13
100%
|
1
100%
|
9
90%
|
39
97.5%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
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%
|
1
10%
|
1
2.5%
|
| Asian |
0
0%
|
0
0%
|
1
7.7%
|
0
0%
|
0
0%
|
1
2.5%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| White |
7
100%
|
9
100%
|
12
92.3%
|
1
100%
|
9
90%
|
38
95%
|
| Other |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (Count of Participants) | ||||||
| United States |
7
100%
|
9
100%
|
13
100%
|
1
100%
|
10
100%
|
40
100%
|
Outcome Measures
| Title | Blood Phenylalanine Concentrations |
|---|---|
| Description | |
| Time Frame | Baseline, Week 1/Day 5, Week 7, Week 16/Day 106 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy Population |
| Arm/Group Title | Starting Dose=0.001 mg/kg | Starting Dose=0.003 mg/kg | Starting Dose=0.01 mg/kg | Starting Dose=0.03 mg/kg | Starting Dose =0.1 mg/kg | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects with starting Dose=0.001 mg/kg | Subjects with starting Dose=0.003 mg/kg | Subjects with starting Dose=0.01 mg/kg | Subjects with starting Dose=0.03 mg/kg | Subjects with starting Dose =0.1 mg/kg | All subjects with different starting dose combined |
| Measure Participants | 7 | 9 | 13 | 1 | 10 | 40 |
| Baseline |
1382.7
(191.40)
|
1336.1
(344.87)
|
1290.5
(459.43)
|
846.0
|
1310.3
(319.01)
|
1310.8
(353.86)
|
| Week 1 Day 5 |
1405.3
(190.87)
|
1276.3
(410.22)
|
1216.5
(434.53)
|
682.0
|
863.7
(307.59)
|
1158.5
(403.63)
|
| Week 7 |
1436.0
(274.08)
|
1324.8
(304.64)
|
1108.7
(510.74)
|
1849.0
|
1321.6
(350.78)
|
1284.5
(405.75)
|
| week 16 Day 106 |
1284.0
(221.73)
|
1049.4
(378.00)
|
1093.5
(445.02)
|
930.7
(331.36)
|
1088.5
(367.67)
|
| Title | Study Drug Related Adverse Events |
|---|---|
| Description | |
| Time Frame | Screening, Weeks 1-22 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population will consist of all subjects who receive any amount of study drug throughout the study duration and have post-treatment safety information (laboratory values, vital signs, adverse events, 12-lead electrocardiogram, antibodies, and physical examinations). |
| Arm/Group Title | Starting Dose=0.001 mg/kg | Starting Dose=0.003 mg/kg | Starting Dose=0.01 mg/kg | Starting Dose=0.03 mg/kg | Starting Dose =0.1 mg/kg | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects with starting Dose=0.001 mg/kg | Subjects with starting Dose=0.003 mg/kg | Subjects with starting Dose=0.01 mg/kg | Subjects with starting Dose=0.03 mg/kg | Subjects with starting Dose =0.1 mg/kg | All subjects with different starting dose combined |
| Measure Participants | 7 | 9 | 13 | 1 | 10 | 40 |
| Count of Participants [Participants] |
5
71.4%
|
9
100%
|
11
84.6%
|
1
100%
|
10
100%
|
36
90%
|
| Title | Number of Participants With Positive PAL IgG Antibody |
|---|---|
| Description | Antibody against PAL (phenylalanine ammonia lyase) measured over time |
| Time Frame | Baseline, Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| safety population |
| Arm/Group Title | Starting Dose=0.001 mg/kg | Starting Dose=0.003 mg/kg | Starting Dose=0.01 mg/kg | Starting Dose=0.03 mg/kg | Starting Dose =0.1 mg/kg | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects with starting Dose=0.001 mg/kg | Subjects with starting Dose=0.003 mg/kg | Subjects with starting Dose=0.01 mg/kg | Subjects with starting Dose=0.03 mg/kg | Subjects with starting Dose =0.1 mg/kg | All subjects with different starting dose combined |
| Measure Participants | 7 | 9 | 13 | 1 | 10 | 40 |
| Baseline |
3
42.9%
|
2
22.2%
|
2
15.4%
|
0
0%
|
0
0%
|
7
17.5%
|
| Week 12 |
7
100%
|
8
88.9%
|
12
92.3%
|
1
100%
|
10
100%
|
38
95%
|
| Title | Number of Participants With Positive PAL IgM Antibody |
|---|---|
| Description | Antibody positivity over time |
| Time Frame | Baseline, Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| safety population |
| Arm/Group Title | Starting Dose=0.001 mg/kg | Starting Dose=0.003 mg/kg | Starting Dose=0.01 mg/kg | Starting Dose=0.03 mg/kg | Starting Dose =0.1 mg/kg | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects with starting Dose=0.001 mg/kg | Subjects with starting Dose=0.003 mg/kg | Subjects with starting Dose=0.01 mg/kg | Subjects with starting Dose=0.03 mg/kg | Subjects with starting Dose =0.1 mg/kg | All subjects with different starting dose combined |
| Measure Participants | 7 | 9 | 13 | 1 | 10 | 40 |
| Baseline |
1
14.3%
|
2
22.2%
|
5
38.5%
|
0
0%
|
4
40%
|
12
30%
|
| Week 12 |
4
57.1%
|
3
33.3%
|
8
61.5%
|
0
0%
|
10
100%
|
25
62.5%
|
| Title | Number of Participants With Positive PEG IgM Antibody |
|---|---|
| Description | Antibody positivity over time |
| Time Frame | Baseline, Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| safety population |
| Arm/Group Title | Starting Dose=0.001 mg/kg | Starting Dose=0.003 mg/kg | Starting Dose=0.01 mg/kg | Starting Dose=0.03 mg/kg | Starting Dose =0.1 mg/kg | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects with starting Dose=0.001 mg/kg | Subjects with starting Dose=0.003 mg/kg | Subjects with starting Dose=0.01 mg/kg | Subjects with starting Dose=0.03 mg/kg | Subjects with starting Dose =0.1 mg/kg | All subjects with different starting dose combined |
| Measure Participants | 7 | 9 | 13 | 1 | 10 | 40 |
| Baseline |
1
14.3%
|
2
22.2%
|
2
15.4%
|
0
0%
|
0
0%
|
5
12.5%
|
| Week 16 |
7
100%
|
7
77.8%
|
8
61.5%
|
0
0%
|
9
90%
|
34
85%
|
| Title | Number of Participants With Positive PEG IgG Antibody |
|---|---|
| Description | Antibody positivity over time |
| Time Frame | Baseline, Week 16 |
Outcome Measure Data
| Analysis Population Description |
|---|
| safety population |
| Arm/Group Title | Starting Dose=0.001 mg/kg | Starting Dose=0.003 mg/kg | Starting Dose=0.01 mg/kg | Starting Dose=0.03 mg/kg | Starting Dose =0.1 mg/kg | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects with starting Dose=0.001 mg/kg | Subjects with starting Dose=0.003 mg/kg | Subjects with starting Dose=0.01 mg/kg | Subjects with starting Dose=0.03 mg/kg | Subjects with starting Dose =0.1 mg/kg | All subjects with different starting dose combined |
| Measure Participants | 7 | 9 | 13 | 1 | 10 | 40 |
| Baseline |
2
28.6%
|
5
55.6%
|
7
53.8%
|
1
100%
|
4
40%
|
19
47.5%
|
| Week 16 |
6
85.7%
|
7
77.8%
|
12
92.3%
|
0
0%
|
9
90%
|
34
85%
|
| Title | Percentage of Participants With Positive Neutralizing Antibodies [NAb] |
|---|---|
| Description | Antibody positivity over time |
| Time Frame | Baseline, Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| safety population |
| Arm/Group Title | Starting Dose=0.001 mg/kg | Starting Dose=0.003 mg/kg | Starting Dose=0.01 mg/kg | Starting Dose=0.03 mg/kg | Starting Dose =0.1 mg/kg | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects with starting Dose=0.001 mg/kg | Subjects with starting Dose=0.003 mg/kg | Subjects with starting Dose=0.01 mg/kg | Subjects with starting Dose=0.03 mg/kg | Subjects with starting Dose =0.1 mg/kg | All subjects with different starting dose combined |
| Measure Participants | 7 | 9 | 13 | 1 | 10 | 40 |
| Baseline |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Week 12 |
0
0%
|
0
0%
|
1
7.7%
|
0
0%
|
3
30%
|
4
10%
|
| Title | Percentage of Participants With Positive PAL IgE Antibody |
|---|---|
| Description | Antibody positivity over time |
| Time Frame | Baselline, Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| safety population |
| Arm/Group Title | Starting Dose=0.001 mg/kg | Starting Dose=0.003 mg/kg | Starting Dose=0.01 mg/kg | Starting Dose=0.03 mg/kg | Starting Dose =0.1 mg/kg | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects with starting Dose=0.001 mg/kg | Subjects with starting Dose=0.003 mg/kg | Subjects with starting Dose=0.01 mg/kg | Subjects with starting Dose=0.03 mg/kg | Subjects with starting Dose =0.1 mg/kg | All subjects with different starting dose combined |
| Measure Participants | 7 | 9 | 13 | 1 | 10 | 40 |
| Baseline |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Week 12 |
1
14.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
2.5%
|
| Title | Percentage of Participants With Positive Anti-PAL-PEG IgE Antibodies |
|---|---|
| Description | Antibody positivity over time |
| Time Frame | Baseline, Week 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| safety population |
| Arm/Group Title | Starting Dose=0.001 mg/kg | Starting Dose=0.003 mg/kg | Starting Dose=0.01 mg/kg | Starting Dose=0.03 mg/kg | Starting Dose =0.1 mg/kg | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects with starting Dose=0.001 mg/kg | Subjects with starting Dose=0.003 mg/kg | Subjects with starting Dose=0.01 mg/kg | Subjects with starting Dose=0.03 mg/kg | Subjects with starting Dose =0.1 mg/kg | All subjects with different starting dose combined |
| Measure Participants | 7 | 9 | 13 | 1 | 10 | 40 |
| Baseline |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Week 12 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Trough Concentration of BMN 165 |
|---|---|
| Description | Plasma concentrations of rAvPAL-PEG (BMN 165) |
| Time Frame | Baseline, Baseline/pre-dose, Week 7, and Week 16/Day 106 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK population will consist of all subjects who received any amount of study drug and have post-treatment plasma BMN 165 concentration measurements. |
| Arm/Group Title | Starting Dose=0.001 mg/kg | Starting Dose=0.003 mg/kg | Starting Dose=0.01 mg/kg | Starting Dose=0.03 mg/kg | Starting Dose =0.1 mg/kg | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Subjects with starting Dose=0.001 mg/kg | Subjects with starting Dose=0.003 mg/kg | Subjects with starting Dose=0.01 mg/kg | Subjects with starting Dose=0.03 mg/kg | Subjects with starting Dose =0.1 mg/kg | All subjects with different starting dose combined |
| Measure Participants | 7 | 9 | 13 | 1 | 10 | 40 |
| Baseline |
0
(0)
|
0
(0)
|
0
(0)
|
0
|
0
(0)
|
|
| Baseline, pre-dose |
1.6
(5.06)
|
1.6
(5.06)
|
||||
| Week 7 |
0
(0)
|
0
(0)
|
0
(0)
|
0
|
0
(0)
|
0
(0)
|
| Week 16-Day 106 |
7.8
(20.52)
|
3.1
(8.70)
|
6.0
(14.54)
|
0
(0)
|
4.2
(12.74)
|
Adverse Events
| Time Frame | Screening- Week 22 | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||
| Arm/Group Title | Starting Dose=0.001 mg/kg | Starting Dose=0.003 mg/kg | Starting Dose=0.01 mg/kg | Starting Dose=0.03 mg/kg | Starting Dose=0.1 mg/kg | |||||
| Arm/Group Description | Subjects will start on rAvPAL-PEG 0.001 mg/kg | Subjects will start on rAvPAL-PEG 0.003 mg/kg | Subjects will start on rAvPAL-PEG 0.01 mg/kg | Subjects will start on rAvPAL-PEG 0.03 mg/kg | Subjects will start on rAvPAL-PEG 0.1 mg/kg | |||||
All Cause Mortality |
||||||||||
| Starting Dose=0.001 mg/kg | Starting Dose=0.003 mg/kg | Starting Dose=0.01 mg/kg | Starting Dose=0.03 mg/kg | Starting Dose=0.1 mg/kg | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/7 (0%) | 0/9 (0%) | 0/13 (0%) | 0/1 (0%) | 0/10 (0%) | |||||
Serious Adverse Events |
||||||||||
| Starting Dose=0.001 mg/kg | Starting Dose=0.003 mg/kg | Starting Dose=0.01 mg/kg | Starting Dose=0.03 mg/kg | Starting Dose=0.1 mg/kg | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/7 (0%) | 0/9 (0%) | 1/13 (7.7%) | 0/1 (0%) | 1/10 (10%) | |||||
| Immune system disorders | ||||||||||
| Hypersensitivity | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||
| Dehydration | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 1/10 (10%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||||||
| Starting Dose=0.001 mg/kg | Starting Dose=0.003 mg/kg | Starting Dose=0.01 mg/kg | Starting Dose=0.03 mg/kg | Starting Dose=0.1 mg/kg | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/7 (100%) | 9/9 (100%) | 13/13 (100%) | 1/1 (100%) | 10/10 (100%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Lymph node pain | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Lymphadenopathy | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 2 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Cardiac disorders | ||||||||||
| Palpitations | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 1/10 (10%) | 1 |
| Sinus bradycardia | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 1/10 (10%) | 1 |
| Tachycardia | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 1/10 (10%) | 1 |
| Ear and labyrinth disorders | ||||||||||
| Middle ear effusion | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Tinnitus | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 1/10 (10%) | 1 |
| Eye disorders | ||||||||||
| Conjunctivitis | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 1/10 (10%) | 1 |
| Eye irritation | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Iritis | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 1/10 (10%) | 1 |
| Vision blurred | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 1/10 (10%) | 1 |
| Gastrointestinal disorders | ||||||||||
| Abdominal discomfort | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Abdominal pain | 0/7 (0%) | 0 | 1/9 (11.1%) | 3 | 3/13 (23.1%) | 3 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Abdominal pain upper | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Constipation | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Diarrhoea | 0/7 (0%) | 0 | 2/9 (22.2%) | 3 | 2/13 (15.4%) | 2 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Flatulence | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Gastrooesophageal reflux disease | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 1/10 (10%) | 1 |
| Gingival bleeding | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 1/10 (10%) | 1 |
| Nausea | 4/7 (57.1%) | 4 | 4/9 (44.4%) | 10 | 4/13 (30.8%) | 5 | 0/1 (0%) | 0 | 1/10 (10%) | 1 |
| Odynophagia | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Vomiting | 1/7 (14.3%) | 1 | 2/9 (22.2%) | 7 | 2/13 (15.4%) | 5 | 0/1 (0%) | 0 | 1/10 (10%) | 1 |
| General disorders | ||||||||||
| Chest discomfort | 0/7 (0%) | 0 | 1/9 (11.1%) | 2 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Chills | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 3/13 (23.1%) | 4 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Fatigue | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 2/10 (20%) | 2 |
| Injection site bruising | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 1/13 (7.7%) | 3 | 0/1 (0%) | 0 | 3/10 (30%) | 3 |
| Injection site dermatitis | 0/7 (0%) | 0 | 2/9 (22.2%) | 2 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Injection site erythema | 1/7 (14.3%) | 3 | 4/9 (44.4%) | 8 | 4/13 (30.8%) | 12 | 0/1 (0%) | 0 | 4/10 (40%) | 5 |
| Injection site haemorrhage | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Injection site nodule | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Injection site pain | 1/7 (14.3%) | 1 | 2/9 (22.2%) | 6 | 1/13 (7.7%) | 2 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Injection site paraesthesia | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 1/10 (10%) | 1 |
| Injection site pruritus | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Injection site rash | 2/7 (28.6%) | 3 | 3/9 (33.3%) | 5 | 2/13 (15.4%) | 6 | 0/1 (0%) | 0 | 3/10 (30%) | 3 |
| Injection site reaction | 1/7 (14.3%) | 2 | 6/9 (66.7%) | 13 | 8/13 (61.5%) | 32 | 0/1 (0%) | 0 | 5/10 (50%) | 20 |
| Injection site swelling | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 2/13 (15.4%) | 15 | 0/1 (0%) | 0 | 2/10 (20%) | 3 |
| Injection site urticaria | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 1/10 (10%) | 1 |
| Non-cardiac chest pain | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Oedema peripheral | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 1/13 (7.7%) | 3 | 0/1 (0%) | 0 | 1/10 (10%) | 1 |
| Pain | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 1/10 (10%) | 2 |
| Pyrexia | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 2/13 (15.4%) | 3 | 0/1 (0%) | 0 | 1/10 (10%) | 1 |
| Immune system disorders | ||||||||||
| Seasonal allergy | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 1/10 (10%) | 1 |
| Infections and infestations | ||||||||||
| Candidiasis | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 1/10 (10%) | 1 |
| Folliculitis | 1/7 (14.3%) | 1 | 1/9 (11.1%) | 1 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Gastroenteritis viral | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Influenza | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Injection site infection | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Lower respiratory tract infection | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Nasopharyngitis | 2/7 (28.6%) | 2 | 2/9 (22.2%) | 2 | 4/13 (30.8%) | 4 | 0/1 (0%) | 0 | 1/10 (10%) | 1 |
| Pharyngitis streptococcal | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Pneumonia | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Sinusitis | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 1/1 (100%) | 1 | 0/10 (0%) | 0 |
| Staphylococcal infection | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Upper respiratory tract infection | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 5/10 (50%) | 5 |
| Urinary tract infection | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Vulvovaginal mycotic infection | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 1/10 (10%) | 1 |
| Injury, poisoning and procedural complications | ||||||||||
| Arthropod sting | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Back injury | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Contusion | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 2/13 (15.4%) | 2 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Excoriation | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Foot fracture | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Joint injury | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 3/10 (30%) | 3 |
| Laceration | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Muscle strain | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 1/10 (10%) | 1 |
| Procedural pain | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Soft tissue injury | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 1/10 (10%) | 1 |
| Sunburn | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Thermal burn | 1/7 (14.3%) | 1 | 1/9 (11.1%) | 1 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Wrist fracture | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Investigations | ||||||||||
| Blood pressure increased | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 1/10 (10%) | 1 |
| Laboratory test abnormal | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Urine analysis abnormal | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||
| Decreased appetite | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 1/13 (7.7%) | 2 | 0/1 (0%) | 0 | 1/10 (10%) | 1 |
| Dehydration | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Increased appetite | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||||
| Arthralgia | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 4/13 (30.8%) | 15 | 0/1 (0%) | 0 | 6/10 (60%) | 8 |
| Arthritis | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Back pain | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 1/10 (10%) | 1 |
| Joint crepitation | 1/7 (14.3%) | 3 | 0/9 (0%) | 0 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Joint effusion | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Joint stiffness | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 2/13 (15.4%) | 2 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Joint swelling | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Muscle twitching | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Musculoskeletal chest pain | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Musculoskeletal pain | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 1/13 (7.7%) | 2 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Myalgia | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 1/10 (10%) | 1 |
| Pain in extremity | 1/7 (14.3%) | 1 | 1/9 (11.1%) | 1 | 2/13 (15.4%) | 5 | 0/1 (0%) | 0 | 1/10 (10%) | 1 |
| Pain in jaw | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Scoliosis | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 1/10 (10%) | 1 |
| Nervous system disorders | ||||||||||
| Cognitive disorder | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Dizziness | 2/7 (28.6%) | 4 | 2/9 (22.2%) | 2 | 3/13 (23.1%) | 5 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Headache | 1/7 (14.3%) | 2 | 5/9 (55.6%) | 6 | 4/13 (30.8%) | 5 | 1/1 (100%) | 1 | 5/10 (50%) | 9 |
| Hypoaesthesia | 1/7 (14.3%) | 2 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Lethargy | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Migraine | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 1/10 (10%) | 1 |
| Paraesthesia | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Poor quality sleep | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Sinus headache | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 2/13 (15.4%) | 2 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Tremor | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Psychiatric disorders | ||||||||||
| Anxiety | 0/7 (0%) | 0 | 1/9 (11.1%) | 2 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 1/10 (10%) | 1 |
| Insomnia | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Libido decreased | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Mood swings | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Reproductive system and breast disorders | ||||||||||
| Vaginal exfoliation | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Cough | 1/7 (14.3%) | 1 | 2/9 (22.2%) | 2 | 1/13 (7.7%) | 2 | 0/1 (0%) | 0 | 2/10 (20%) | 2 |
| Dyspnoea | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Hiccups | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Nasal congestion | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Oropharyngeal pain | 1/7 (14.3%) | 1 | 2/9 (22.2%) | 2 | 3/13 (23.1%) | 3 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Pulmonary congestion | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Rhinitis seasonal | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Rhinorrhoea | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Throat irritation | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Throat tightness | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 2 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Wheezing | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||
| Dermal cyst | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Dermatitis contact | 0/7 (0%) | 0 | 2/9 (22.2%) | 3 | 2/13 (15.4%) | 2 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Dermatitis exfoliative | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Dry skin | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Ecchymosis | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Erythema | 0/7 (0%) | 0 | 2/9 (22.2%) | 2 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Pain of skin | 1/7 (14.3%) | 1 | 0/9 (0%) | 0 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Petechiae | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 1/10 (10%) | 1 |
| Pruritus | 0/7 (0%) | 0 | 2/9 (22.2%) | 3 | 3/13 (23.1%) | 3 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Pruritus generalised | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Rash | 2/7 (28.6%) | 2 | 3/9 (33.3%) | 5 | 2/13 (15.4%) | 2 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Rash erythematous | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Rash generalised | 1/7 (14.3%) | 1 | 1/9 (11.1%) | 1 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 3/10 (30%) | 3 |
| Skin reaction | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 0/13 (0%) | 0 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Urticaria | 0/7 (0%) | 0 | 1/9 (11.1%) | 1 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 1/10 (10%) | 1 |
| Surgical and medical procedures | ||||||||||
| Myomectomy | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 1 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
| Vascular disorders | ||||||||||
| Pallor | 0/7 (0%) | 0 | 0/9 (0%) | 0 | 1/13 (7.7%) | 2 | 0/1 (0%) | 0 | 0/10 (0%) | 0 |
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 | Medical Director |
|---|---|
| Organization | BioMarin Pharmaceutical Inc. |
| Phone | 415-475-5854 |
| ari.gershman@bmrn.com |
Responsible Party:
BioMarin Pharmaceutical
ClinicalTrials.gov Identifier:
NCT00925054
Other Study ID Numbers:
- PAL-002
First Posted:
Jun 19, 2009
Last Update Posted:
Feb 26, 2019
Last Verified:
Feb 1, 2019