Prism-2: Phase 3 Study to Evaluate the Efficacy & Safety of Self-Administered Injections of BMN165 by Adults With PKU
Sponsor
BioMarin Pharmaceutical (Industry)
Overall Status
Completed
CT.gov ID
NCT01889862
Collaborator
(none)
215
29
4
66.3
7.4
0.1
Study Details
Study Description
Brief Summary
The BMN 165 clinical development program has been designed to demonstrate the safety and efficacy of BMN 165 in reducing blood Phe concentrations in adults with PKU.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
165-302 is a Phase 3, 4 Part, Randomized, Double-Blind, Placebo-Controlled, Discontinuation Study to Evaluate the Efficacy and Safety of Self Administered Subcutaneous Injections of BMN 165 by Adults With PKU.
This study is open only to adults who have been exposed to BMN165 in a previous study.
Study BMN 165-302 is a four-Part, Phase 3 study.
-
Part 1: Open-label period
-
Part 2: A Randomized, double-blind, placebo-controlled period of 8 weeks
-
Part 3: Two sub-Parts to Part 3:- Part 3A - BMN 165 administered using vial and syringe during this open label period. Part 3B - BMN 165 administered using prefilled syringe during this open-label period.
-
Part 4: A long-term, open-label extension period.
Study Design
Study Type:
Interventional
Actual Enrollment
:
215 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
A Four-Part, Phase 3, Randomized, Double-Blind, Placebo- Controlled, Four-Arm, Discontinuation Study to Evaluate the Efficacy and Safety of Subcutaneous Injections of BMN 165 Self-Administered by Adults With Phenylketonuria (PKU)
Actual Study Start Date
:
Jul 29, 2013
Actual Primary Completion Date
:
Jan 13, 2016
Actual Study Completion Date
:
Feb 5, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: BMN165 20mg/day BMN165 20mg/day self-administered daily |
Drug: BMN165 20mg/day
BMN165 20mg/day self-administered daily
Other Names:
|
| Placebo Comparator: 20 mg/day Placebo 20 mg/day Placebo self-administered daily |
Drug: Placebo
Non-drug placebo, self-administered daily
Other Names:
|
| Active Comparator: BMN165 40mg/day BMN165 40mg/day self-administered daily |
Drug: BMN165 40mg/day
BMN165 40mg/day self-administered daily
Other Names:
|
| Placebo Comparator: 40 mg/day Placebo 40 mg/day Placebo self-administered daily |
Drug: Placebo
Non-drug placebo, self-administered daily
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 2 [At Part 2 baseline and change from baseline at Part 2 week 8]
Blood phe concentration in subjects previously exposed to BMN165 who were administered BMN165 20 or 40 mg/day compared with those who were administered a matching placebo.
Secondary Outcome Measures
- Change From Baseline in the Cognitive and Mood Symptoms Measured by ADHD Rating Scale (RS)-IV Inattention Subscale at Part 2 [At Part 2 baseline and change from baseline at Part 2 week 8]
Attention deficit hyperactivity disorder rating scale IV (ADHD RS-IV) is investigator-rated, 9-item, inattention subscale score ranges from 0 to 27, with higher scores indicative of a greater degree of impairment and a baseline score >9 indicative of a presence of symptoms.
- Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 4 [At Part 4 week 57, 105, 161, 209 and 249]
The long term effect of multiple dose levels of BMN165 on blood phe concentration in subjects who are administered BMN165 using pre-filled syringes.
- Change From Baseline in the Cognitive and Mood Symptoms Measured by PKU POMS TMD at Part 2 [At Part 2 baseline and change from baseline at Part 2 week 8]
Phenylketonuria (PKU) Total Mood Disturbance (TMD) Profile of Mood States (POMS) PKU POMS TMD is self-rated, each item in the tool is rated using a five-point Likert scale: 0 (not at all), 1 (a little), 2 (moderately), 3 (quite a bit), and 4 (extremely).
- Change From Baseline in the Cognitive and Mood Symptoms Measured by PKU POMS Confusion Subscale at Part 2 [At Part 2 baseline and change from baseline at Part 2 week 8]
PKU POMS confusion mood domain (referred to as the confusion subscale) is self-rated, each item in the tool is rated using a five-point Likert scale: 0 (not at all), 1 (a little), 2 (moderately), 3 (quite a bit), and 4 (extremely).
- Change From Baseline in the Cognitive and Mood Symptoms Measured by POMS TMD at Part 2 [At Part 2 baseline and change from baseline at Part 2 week 8]
Full-length POMS TMD is self-rated, each item in the tool is rated using a five-point Likert scale: 0 (not at all), 1 (a little), 2 (moderately), 3 (quite a bit), and 4 (extremely).
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
INCLUSION CRITERIA
Individuals eligible to participate in this study must meet all of the following criteria:
-
Have completed a prior BMN 165 study (PAL-003, 165-205, or 165-301) prior to screening
-
Have had a stable BMN 165 dose regimen for at least 14 days prior to screening
-
Are at least 18 y/o and no older than 70 y/o at screening
-
Subjects who are < 18 y/o and are already enrolled into Study 165-301 under Amendment #1 (10JAN2014) may enroll into this study
-
Has identified a person who is > 18 y/o who has the neurocognitive and linguistic capacities to comprehend and complete the Profile of Mood States (POMS)-Observer rated scale
-
Has identified a competent person(s) > 18 y/o who can observe the subject during study drug administration at certain points in the study
-
A home healthcare nurse may perform the study drug observations
-
Are willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to any research-related procedures; for minors, parent or guardian provides written consent and assent may be requested
-
Are willing and able to comply with all study procedures
-
For females of childbearing potential, a negative pregnancy test at screening and willing to have additional pregnancy tests during the study
-
If sexually active, willing to use two acceptable methods of contraception during and for 4 weeks after the study
-
Males post vasectomy for 2 years with no known pregnancies do not need to use any other forms of contraception during the study.
-
Females who have been in menopause for at least 2 years, have had a tubal ligation at least 1 year prior to screening, or have had a total hysterectomy do not need to use any other forms of contraception during the study.
-
Have received documented approval from a study dietitian confirming that the subject is capable of maintaining their diet
-
Have neurocognitive and linguistic capacities to comprehend and answer investigator's prompts for the Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS) Investigator rated instrument and to complete the POMS-Subject rated scale
-
If applicable, maintained stable dose of medication for Attention Deficit Hyperactivity Disorder (ADHD), depression, anxiety, or other psychiatric disorder ≥8 weeks prior to enrollment and willing to maintain stable dose throughout study unless a change is medically indicated
-
General good health, as evidenced by physical examination, clinical laboratory evaluations, and ECG tests at screening
Exclusion Criteria
Individuals who meet any of the following exclusion criteria will not be eligible to participate in the study:
-
Use of any investigational product (except BMN 165) 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 (except BMN 165) intended to treat PKU, including the use of large neutral amino acids, within 2 days prior to the administration of study drug
-
Have known hypersensitivity to Dextran® or components of Dextran
-
Use or planned use of any injectable drugs containing PEG (except for BMN 165), including medroxyprogesterone injection, within 3 months prior to screening and during study participation
-
Current use of levodopa
-
A positive test for HIV antibody, hepatitis B surface antigen, or hepatitis C antibody
-
A history of organ transplantation or taking chronic immunosuppressive therapy
-
A history of substance abuse in the past 12 months or current alcohol or drug abuse
-
Current participation in the Kuvan registry study (PKUDOS). Patients may discontinue the PKUDOS registry trial to allow enrollment in this study
-
Pregnant or breastfeeding at screening or planning to become pregnant (self or partner) or breastfeed at any time during the study
-
Concurrent disease or condition that would interfere with study participation or safety.
-
Major surgery planned during the study period
-
Any condition that in the view of the investigator, places the subject at high risk of poor treatment compliance or terminating early from the study
-
Alanine aminotransferase (ALT) concentration at least 2x the upper limit of normal
-
Creatinine at least 1.5x the upper limit of normal
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of California, San Diego Clinical and Translational Research Institute | La Jolla | California | United States | 92093 |
| 2 | UCSF Benioff Children's Hospital Oakland | Oakland | California | United States | 94609 |
| 3 | Children's Hospital Colorado | Aurora | Colorado | United States | 80045 |
| 4 | University of Florida Clinical Research Center | Gainesville | Florida | United States | 32610 |
| 5 | University of South Florida | Tampa | Florida | United States | 33606 |
| 6 | Emory Universty, Department of Human Genetics, Division of Medical Genetics | Atlanta | Georgia | United States | 30322 |
| 7 | Ann and Robert H Lurie Children's Hospital of Chicago | Chicago | Illinois | United States | 60611 |
| 8 | Indiana CTSI Clinical Research Center | Indianapolis | Indiana | United States | 46202 |
| 9 | University of Kentucky Medical Center | Lexington | Kentucky | United States | 40536 |
| 10 | University of Louisville, Kosair Charities Pediatric Clinical Research Unit | Louisville | Kentucky | United States | 40202 |
| 11 | Boston Children's Hospital | Boston | Massachusetts | United States | 02115 |
| 12 | Wayne State University Clinical Research Center at the Mott Center | Detroit | Michigan | United States | 48202 |
| 13 | University of Missouri Health Center | Columbia | Missouri | United States | 65212 |
| 14 | Washington University Center for Applied Research Sciences | Saint Louis | Missouri | United States | 63110 |
| 15 | University of Nebraska Medical Center | Omaha | Nebraska | United States | 68198 |
| 16 | Cooper Health Systems | Camden | New Jersey | United States | 08103 |
| 17 | Atlantic Health System - Morristown Medical Center | Morristown | New Jersey | United States | 07960 |
| 18 | Albany Medical Center | Albany | New York | United States | 12208 |
| 19 | Icahn School of Medicine at Mount Sinai Medical Center | New York | New York | United States | 10029 |
| 20 | University Hospitals Case Medical Center | Cleveland | Ohio | United States | 44106 |
| 21 | University of Oklahoma Health Sciences Center | Oklahoma City | Oklahoma | United States | 73104 |
| 22 | Oregon Health and Science University | Portland | Oregon | United States | 97239 |
| 23 | St. Christopher's Hospital for Children | Philadelphia | Pennsylvania | United States | 19134 |
| 24 | Children's Hospital of Pittsburgh, University of Pittsburgh Medical Center | Pittsburgh | Pennsylvania | United States | 15224 |
| 25 | Vanderbilt Children's Hospital | Nashville | Tennessee | United States | 37232 |
| 26 | University of Texas Houston Medical School | Houston | Texas | United States | 77030 |
| 27 | University of Utah Hospital | Salt Lake City | Utah | United States | 84108 |
| 28 | University of Washinton | Seattle | Washington | United States | 98195 |
| 29 | Medical College of Wisconsin | Milwaukee | Wisconsin | United States | 53226 |
Sponsors and Collaborators
- BioMarin Pharmaceutical
Investigators
- Study Director: Clinical Trial Specialist, BioMarin Pharmaceutical
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
BioMarin Pharmaceutical
ClinicalTrials.gov Identifier:
NCT01889862
Other Study ID Numbers:
- 165-302
First Posted:
Jul 1, 2013
Last Update Posted:
May 21, 2021
Last Verified:
Apr 1, 2021
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 | This was a multicenter study, conducted in 29 study centers of United States. |
|---|---|
| Pre-assignment Detail | A total of 51 out of 215 subjects entered Part 4 directly from 165-301, as they did not receive target dose of 20 or 40 mg/day in 165-301. |
| Arm/Group Title | BMN165 20mg/Day | Placebo 20mg/Day | BMN165 40mg/Day | Placebo 40mg/Day | BMN165 |
|---|---|---|---|---|---|
| Arm/Group Description | BMN165 20mg/day subcutaneous injection administered using vial and syringe in Part 1, 2 and 3A. BMN165 20mg/day subcutaneous injection administered using a prefilled syringe in Part 3B. | Matching placebo 20mg/day subcutaneous injection administered using vial and syringe in Part 2. | BMN165 40mg/day subcutaneous injection administered using vial and syringe in Part 1, 2 and 3A. BMN165 40mg/day subcutaneous injection administered using a prefilled syringe in Part 3B. | Matching placebo 40mg/day subcutaneous injection administered using vial and syringe in Part 2. | Up to 60mg/day BMN165 subcutaneous injection administered using a prefilled syringe in Part 4. |
| Period Title: Part 1 (Up to 13 Weeks) | |||||
| STARTED | 86 | 0 | 78 | 0 | 0 |
| COMPLETED | 74 | 0 | 78 | 0 | 0 |
| NOT COMPLETED | 12 | 0 | 0 | 0 | 0 |
| Period Title: Part 1 (Up to 13 Weeks) | |||||
| STARTED | 34 | 15 | 32 | 14 | 0 |
| Per Amendment #2 of the Protocol | 29 | 14 | 29 | 14 | 0 |
| COMPLETED | 34 | 15 | 31 | 14 | 0 |
| NOT COMPLETED | 0 | 0 | 1 | 0 | 0 |
| Period Title: Part 1 (Up to 13 Weeks) | |||||
| STARTED | 48 | 0 | 41 | 0 | 0 |
| Per Amendment #2 of the Protocol | 34 | 0 | 26 | 0 | 0 |
| COMPLETED | 48 | 0 | 41 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 |
| Period Title: Part 1 (Up to 13 Weeks) | |||||
| STARTED | 0 | 0 | 0 | 0 | 202 |
| COMPLETED | 0 | 0 | 0 | 0 | 172 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 30 |
Baseline Characteristics
| Arm/Group Title | All Subjects |
|---|---|
| Arm/Group Description | BMN165 20mg/Day: BMN165 20mg/day subcutaneous injection administered using vial and syringe in Part 1, 2 and 3A. BMN165 20mg/day subcutaneous injection administered using a prefilled syringe in Part 3B. Placebo 20mg/Day: Matching placebo 20mg/day subcutaneous injection administered using vial and syringe in Part 2. BMN165 40mg/Day: BMN165 40mg/day subcutaneous injection administered using vial and syringe in Part 1, 2 and 3A. BMN165 40mg/day subcutaneous injection administered using a prefilled syringe in Part 3B. Placebo 40mg/Day: Matching placebo 40mg/day subcutaneous injection administered using vial and syringe in Part 2. BMN165: Up to 60mg/day BMN165 subcutaneous injection administered using a prefilled syringe in Part 4. |
| Overall Participants | 215 |
| Age (yrs) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [yrs] |
29.22
(8.74)
|
| Age, Customized (Count of Participants) | |
| 16 - <18 years |
11
5.1%
|
| 18 - <66 years |
204
94.9%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
105
48.8%
|
| Male |
110
51.2%
|
| Race/Ethnicity, Customized (Count of Participants) | |
| American Indian or Alaska Native |
1
0.5%
|
| White |
211
98.1%
|
| Black/African American |
2
0.9%
|
Outcome Measures
| Title | Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 2 |
|---|---|
| Description | Blood phe concentration in subjects previously exposed to BMN165 who were administered BMN165 20 or 40 mg/day compared with those who were administered a matching placebo. |
| Time Frame | At Part 2 baseline and change from baseline at Part 2 week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Modified Intent-to-Treat (mITT) population consists of all subjects who reached the randomized dose of 20mg/day or 40mg/day and were randomized into Part 2 with a mean blood Phe reduction of ≥20% (using the last two consecutive blood Phe assessments of Part 1) from the baseline of 165-301 (or the Phase 2 study in which they initiated BMN165). |
| Arm/Group Title | BMN165 20mg/Day | Placebo 20mg/Day | BMN165 40mg/Day | Placebo 40mg/Day |
|---|---|---|---|---|
| Arm/Group Description | BMN165 20mg/day subcutaneous injection administered using vial and syringe in Part 1, 2 and 3A. BMN165 20mg/day subcutaneous injection administered using a prefilled syringe in Part 3B. | Matching placebo 20mg/day subcutaneous injection administered using vial and syringe in Part 2. | BMN165 40mg/day subcutaneous injection administered using vial and syringe in Part 1, 2 and 3A. BMN165 40mg/day subcutaneous injection administered using a prefilled syringe in Part 3B. | Matching placebo 40mg/day subcutaneous injection administered using vial and syringe in Part 2. |
| Measure Participants | 29 | 14 | 29 | 14 |
| Part 2 Baseline |
596.8
(582.75)
|
563.9
(504.62)
|
410.9
(439.95)
|
508.2
(363.68)
|
| Change from Baseline Part 2 Week 8 |
-65.9
(192.02)
|
996.4
(555.00)
|
114.1
(332.40)
|
599.0
(507.40)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | BMN165 20mg/Day, Placebo 20mg/Day |
|---|---|---|
| Comments | Change in blood Phe concentration during Part 2 in subjects previously exposed to BMN165 who self administer BMN165 20mg/day compared with those who self administer matching placebo. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | Based on Mixed-Effect Model Repeated Measure (MMRM) model with change from baseline as the response variable, and treatment, visit and treatment by visit interaction and baseline blood phe concentration as factors. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -973.02 | |
| Confidence Interval |
(2-Sided) 95% -1204.19 to -741.85 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | BMN165 40mg/Day, Placebo 40mg/Day |
|---|---|---|
| Comments | Change in blood Phe concentration during Part 2 in subjects previously exposed to BMN165 who self administer BMN165 40mg/day compared with those who self administer matching placebo. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | Based on Mixed-Effect Model Repeated Measure (MMRM) model with change from baseline as the response variable, and treatment, visit and treatment by visit interaction and baseline blood phe concentration as factors. | |
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | -588.50 | |
| Confidence Interval |
(2-Sided) 95% -830.07 to -346.94 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change From Baseline in the Cognitive and Mood Symptoms Measured by ADHD Rating Scale (RS)-IV Inattention Subscale at Part 2 |
|---|---|
| Description | Attention deficit hyperactivity disorder rating scale IV (ADHD RS-IV) is investigator-rated, 9-item, inattention subscale score ranges from 0 to 27, with higher scores indicative of a greater degree of impairment and a baseline score >9 indicative of a presence of symptoms. |
| Time Frame | At Part 2 baseline and change from baseline at Part 2 week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT population |
| Arm/Group Title | BMN165 20mg/Day | Placebo 20mg/Day | BMN165 40mg/Day | Placebo 40mg/Day |
|---|---|---|---|---|
| Arm/Group Description | BMN165 20mg/day subcutaneous injection administered using vial and syringe in Part 1, 2 and 3A. BMN165 20mg/day subcutaneous injection administered using a prefilled syringe in Part 3B. | Matching placebo 20mg/day subcutaneous injection administered using vial and syringe in Part 2. | BMN165 40mg/day subcutaneous injection administered using vial and syringe in Part 1, 2 and 3A. BMN165 40mg/day subcutaneous injection administered using a prefilled syringe in Part 3B. | Matching placebo 40mg/day subcutaneous injection administered using vial and syringe in Part 2. |
| Measure Participants | 29 | 14 | 29 | 14 |
| Baseline |
5.9
(4.70)
|
5.0
(4.26)
|
6.0
(6.45)
|
2.9
(3.68)
|
| Change from Baseline Part 2 Week 8 |
1.1
(3.96)
|
1.2
(3.00)
|
0.5
(5.36)
|
-0.4
(3.44)
|
| Title | Change From Baseline in the Blood Plasma Phenylalanine (Phe) Concentration at Part 4 |
|---|---|
| Description | The long term effect of multiple dose levels of BMN165 on blood phe concentration in subjects who are administered BMN165 using pre-filled syringes. |
| Time Frame | At Part 4 week 57, 105, 161, 209 and 249 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All Subjects Entered 165-302 Part 4 Data |
| Arm/Group Title | BMN165 < 20 mg/Day - Part 4 | BMN165 20 to < 40 mg/Day - Part 4 | BMN165 40 to < 60 mg/Day - Part 4 | BMN165 >= 60 mg/Day - Part 4 | BMN165 All Dose - Part 4 |
|---|---|---|---|---|---|
| Arm/Group Description | BMN165 < 20 mg/day subcutaneous injection administered using a prefilled syringe in Part 4. | BMN165 < 20 mg/day subcutaneous injection administered using a prefilled syringe in Part 4. | BMN165 40 to < 60 mg/day subcutaneous injection administered using a prefilled syringe in Part 4. | BMN165 >= 60 mg/day subcutaneous injection administered using a prefilled syringe in Part 4. | Up to 60mg/day BMN165 subcutaneous injection administered using a prefilled syringe in Part 4. |
| Measure Participants | 61 | 131 | 184 | 62 | 202 |
| Change from Baseline to Part 4 Week 57 |
-1004.9
(541.19)
|
-984.0
(531.33)
|
-810.2
(595.24)
|
-662.3
(465.61)
|
-839.5
(562.74)
|
| Change from Baseline to Part 4 Week 105 |
-1015.3
(557.00)
|
-1109.2
(474.25)
|
-858.5
(593.73)
|
-641.0
(568.67)
|
-890.8
(578.38)
|
| Change from Baseline to Part 4 Week 161 |
-1006.5
(514.76)
|
-1111.9
(519.40)
|
-662.8
(433.80)
|
-808.6
(558.22)
|
-882.0
(528.61)
|
| Change from Baseline to Part 4 Week 209 |
-897.3
(494.41)
|
-1020.4
(495.79)
|
-541.6
(245.83)
|
-961.7
(339.92)
|
-842.3
(418.37)
|
| Change from Baseline to Part 4 Week 249 |
-1059.5
(160.51)
|
-1314.0
(NA)
|
-1144.3
(185.67)
|
| Title | Change From Baseline in the Cognitive and Mood Symptoms Measured by PKU POMS TMD at Part 2 |
|---|---|
| Description | Phenylketonuria (PKU) Total Mood Disturbance (TMD) Profile of Mood States (POMS) PKU POMS TMD is self-rated, each item in the tool is rated using a five-point Likert scale: 0 (not at all), 1 (a little), 2 (moderately), 3 (quite a bit), and 4 (extremely). |
| Time Frame | At Part 2 baseline and change from baseline at Part 2 week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT population |
| Arm/Group Title | BMN165 20mg/Day | Placebo 20mg/Day | BMN165 40mg/Day | Placebo 40mg/Day |
|---|---|---|---|---|
| Arm/Group Description | BMN165 20mg/day subcutaneous injection administered using vial and syringe in Part 1, 2 and 3A. BMN165 20mg/day subcutaneous injection administered using a prefilled syringe in Part 3B. | Matching placebo 20mg/day subcutaneous injection administered using vial and syringe in Part 2. | BMN165 40mg/day subcutaneous injection administered using vial and syringe in Part 1, 2 and 3A. BMN165 40mg/day subcutaneous injection administered using a prefilled syringe in Part 3B. | Matching placebo 40mg/day subcutaneous injection administered using vial and syringe in Part 2. |
| Measure Participants | 29 | 14 | 29 | 14 |
| Baseline |
7.1
(14.18)
|
8.6
(10.84)
|
8.9
(12.28)
|
5.0
(8.56)
|
| Change from Baseline Part 2 Week 8 |
4.8
(12.63)
|
4.3
(11.96)
|
-2.0
(10.25)
|
0.0
(14.08)
|
| Title | Change From Baseline in the Cognitive and Mood Symptoms Measured by PKU POMS Confusion Subscale at Part 2 |
|---|---|
| Description | PKU POMS confusion mood domain (referred to as the confusion subscale) is self-rated, each item in the tool is rated using a five-point Likert scale: 0 (not at all), 1 (a little), 2 (moderately), 3 (quite a bit), and 4 (extremely). |
| Time Frame | At Part 2 baseline and change from baseline at Part 2 week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT population |
| Arm/Group Title | BMN165 20mg/Day | Placebo 20mg/Day | BMN165 40mg/Day | Placebo 40mg/Day |
|---|---|---|---|---|
| Arm/Group Description | BMN165 20mg/day subcutaneous injection administered using vial and syringe in Part 1, 2 and 3A. BMN165 20mg/day subcutaneous injection administered using a prefilled syringe in Part 3B. | Matching placebo 20mg/day subcutaneous injection administered using vial and syringe in Part 2. | BMN165 40mg/day subcutaneous injection administered using vial and syringe in Part 1, 2 and 3A. BMN165 40mg/day subcutaneous injection administered using a prefilled syringe in Part 3B. | Matching placebo 40mg/day subcutaneous injection administered using vial and syringe in Part 2. |
| Measure Participants | 29 | 14 | 29 | 14 |
| Baseline |
2.0
(2.09)
|
2.1
(1.49)
|
2.4
(2.02)
|
1.2
(1.53)
|
| Change from Baseline Part 2 Week 8 |
0.8
(2.79)
|
1.4
(2.47)
|
-0.3
(1.84)
|
0.5
(2.22)
|
| Title | Change From Baseline in the Cognitive and Mood Symptoms Measured by POMS TMD at Part 2 |
|---|---|
| Description | Full-length POMS TMD is self-rated, each item in the tool is rated using a five-point Likert scale: 0 (not at all), 1 (a little), 2 (moderately), 3 (quite a bit), and 4 (extremely). |
| Time Frame | At Part 2 baseline and change from baseline at Part 2 week 8 |
Outcome Measure Data
| Analysis Population Description |
|---|
| mITT population |
| Arm/Group Title | BMN165 20mg/Day | Placebo 20mg/Day | BMN165 40mg/Day | Placebo 40mg/Day |
|---|---|---|---|---|
| Arm/Group Description | BMN165 20mg/day subcutaneous injection administered using vial and syringe in Part 1, 2 and 3A. BMN165 20mg/day subcutaneous injection administered using a prefilled syringe in Part 3B. | Matching placebo 20mg/day subcutaneous injection administered using vial and syringe in Part 2. | BMN165 40mg/day subcutaneous injection administered using vial and syringe in Part 1, 2 and 3A. BMN165 40mg/day subcutaneous injection administered using a prefilled syringe in Part 3B. | Matching placebo 40mg/day subcutaneous injection administered using vial and syringe in Part 2. |
| Measure Participants | 29 | 14 | 29 | 14 |
| Baseline |
16.2
(35.63)
|
18.1
(28.26)
|
24.3
(35.38)
|
13.3
(21.63)
|
| Change from Baseline Part 2 Week 8 |
13.1
(30.73)
|
7.3
(26.23)
|
-3.2
(26.63)
|
-1.7
(29.34)
|
Adverse Events
| Time Frame | Up to 301 weeks | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Safety Analyses consists of the population for safety analyses of all subjects who enrolled into the study and all subjects who enrolled into each study part for analysis by study part. | |||||||||||||||||||||||||||
| Arm/Group Title | Part 1 - 20 mg/Day | Part 1 - 40 mg/Day | Part 2 - 20 mg/Day Active | Part 2 - 40 mg/Day Active | Part 2 - 20 mg/Day Placebo | Part 2 - 40 mg/Day Placebo | Part 3 - Stay on Active 20 mg/Day | Part 3 - Stay on Active 40 mg/Day | Part 3 - Switch From Placebo to Active 20 mg/Day | Part 3 - Switch From Placebo to Active 40 mg/Day | Part 4 - < 20 mg/Day | Part 4 - 20 to < 40 mg/Day | Part 4 - 40 to < 60 mg/Day | Part 4 - >= 60 mg/Day | ||||||||||||||
| Arm/Group Description | BMN165 20mg/day subcutaneous injection administered using vial and syringe. | BMN165 40mg/day subcutaneous injection administered using vial and syringe. | BMN165 20mg/day subcutaneous injection administered using vial and syringe. | BMN165 40mg/day subcutaneous injection administered using vial and syringe. | Matching placebo 20mg/day subcutaneous injection administered using vial and syringe. | Matching placebo 40mg/day subcutaneous injection administered using vial and syringe. | BMN165 20mg/day subcutaneous injection administered using vial and syringe in Part 3A. BMN165 20mg/day subcutaneous injection administered using a prefilled syringe in Part 3B. | BMN165 40mg/day subcutaneous injection administered using vial and syringe in Part 3A. BMN165 40mg/day subcutaneous injection administered using a prefilled syringe in Part 3B. | BMN165 20mg/day subcutaneous injection administered using vial and syringe in Part 3A. BMN165 20mg/day subcutaneous injection administered using a prefilled syringe in Part 3B. | BMN165 40mg/day subcutaneous injection administered using vial and syringe in Part 3A. BMN165 40mg/day subcutaneous injection administered using a prefilled syringe in Part 3B. | BMN165 <20mg/day subcutaneous injection administered using a prefilled syringe. | BMN165 20 to <40mg/day subcutaneous injection administered using a prefilled syringe. | BMN165 40 to <60mg/day subcutaneous injection administered using a prefilled syringe. | BMN165 >=60mg/day subcutaneous injection administered using a prefilled syringe. | ||||||||||||||
All Cause Mortality |
||||||||||||||||||||||||||||
| Part 1 - 20 mg/Day | Part 1 - 40 mg/Day | Part 2 - 20 mg/Day Active | Part 2 - 40 mg/Day Active | Part 2 - 20 mg/Day Placebo | Part 2 - 40 mg/Day Placebo | Part 3 - Stay on Active 20 mg/Day | Part 3 - Stay on Active 40 mg/Day | Part 3 - Switch From Placebo to Active 20 mg/Day | Part 3 - Switch From Placebo to Active 40 mg/Day | Part 4 - < 20 mg/Day | Part 4 - 20 to < 40 mg/Day | Part 4 - 40 to < 60 mg/Day | Part 4 - >= 60 mg/Day | |||||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
Serious Adverse Events |
||||||||||||||||||||||||||||
| Part 1 - 20 mg/Day | Part 1 - 40 mg/Day | Part 2 - 20 mg/Day Active | Part 2 - 40 mg/Day Active | Part 2 - 20 mg/Day Placebo | Part 2 - 40 mg/Day Placebo | Part 3 - Stay on Active 20 mg/Day | Part 3 - Stay on Active 40 mg/Day | Part 3 - Switch From Placebo to Active 20 mg/Day | Part 3 - Switch From Placebo to Active 40 mg/Day | Part 4 - < 20 mg/Day | Part 4 - 20 to < 40 mg/Day | Part 4 - 40 to < 60 mg/Day | Part 4 - >= 60 mg/Day | |||||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/86 (7%) | 2/78 (2.6%) | 0/34 (0%) | 2/32 (6.3%) | 1/15 (6.7%) | 0/14 (0%) | 1/23 (4.3%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 7/67 (10.4%) | 6/152 (3.9%) | 16/186 (8.6%) | 5/89 (5.6%) | ||||||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||||||||
| Iron Deficiency Anaemia | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 0/186 (0%) | 1/89 (1.1%) | ||||||||||||||
| Lymphoid Tissue Hyperplasia | 1/86 (1.2%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
| Cardiac disorders | ||||||||||||||||||||||||||||
| Tachycardia | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 0/186 (0%) | 1/89 (1.1%) | ||||||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||||||||||
| Epiploic Appendagitis | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 1/186 (0.5%) | 0/89 (0%) | ||||||||||||||
| Haemorrhoidal Haemorrhage | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 1/152 (0.7%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
| Haemorrhoids | 1/86 (1.2%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
| Pancreatitis | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 1/152 (0.7%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
| General disorders | ||||||||||||||||||||||||||||
| Chest Pain | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 2/186 (1.1%) | 0/89 (0%) | ||||||||||||||
| Non-cardiac Chest Pain | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 2/186 (1.1%) | 0/89 (0%) | ||||||||||||||
| Immune system disorders | ||||||||||||||||||||||||||||
| Anaphylactic Reaction | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 1/152 (0.7%) | 4/186 (2.2%) | 0/89 (0%) | ||||||||||||||
| Anaphylactoid Reaction | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 1/186 (0.5%) | 0/89 (0%) | ||||||||||||||
| Hypersensitivity | 0/86 (0%) | 1/78 (1.3%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 1/152 (0.7%) | 2/186 (1.1%) | 0/89 (0%) | ||||||||||||||
| Infections and infestations | ||||||||||||||||||||||||||||
| Appendicitis | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 1/186 (0.5%) | 0/89 (0%) | ||||||||||||||
| Cellulitis | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 1/186 (0.5%) | 0/89 (0%) | ||||||||||||||
| Diverticulitis | 1/86 (1.2%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
| Pneumonia | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 0/186 (0%) | 1/89 (1.1%) | ||||||||||||||
| Soft Tissue Infection | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 1/152 (0.7%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||||||||||||
| Road Traffic Accident | 0/86 (0%) | 1/78 (1.3%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 2/67 (3%) | 0/152 (0%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
| Post procedural haematoma | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 1/152 (0.7%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
| Tendon injury | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 1/152 (0.7%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
| Investigations | ||||||||||||||||||||||||||||
| Blood creatine phosphokinase increased | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 1/15 (6.7%) | 0/14 (0%) | 1/23 (4.3%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 1/67 (1.5%) | 0/152 (0%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
| Blood pressure increased | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 1/67 (1.5%) | 0/152 (0%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||||||
| Arthralgia | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 1/152 (0.7%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
| Back pain | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 1/152 (0.7%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
| Scoliosis | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 0/186 (0%) | 1/89 (1.1%) | ||||||||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||||||||
| Appendix Adenoma | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 0/186 (0%) | 1/89 (1.1%) | ||||||||||||||
| Xanthogranuloma | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 1/186 (0.5%) | 0/89 (0%) | ||||||||||||||
| Nervous system disorders | ||||||||||||||||||||||||||||
| Loss of consciousness | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 1/152 (0.7%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
| Migraine | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 1/186 (0.5%) | 0/89 (0%) | ||||||||||||||
| Presyncope | 1/86 (1.2%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
| Pregnancy, puerperium and perinatal conditions | ||||||||||||||||||||||||||||
| Abortion missed | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 1/67 (1.5%) | 0/152 (0%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
| Gestational hypertension | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 1/67 (1.5%) | 0/152 (0%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
| Hyperemesis gravidarum | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 1/186 (0.5%) | 0/89 (0%) | ||||||||||||||
| Psychiatric disorders | ||||||||||||||||||||||||||||
| Agitation | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 1/32 (3.1%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
| Depression | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 1/32 (3.1%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 1/152 (0.7%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
| Anxiety | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 1/186 (0.5%) | 0/89 (0%) | ||||||||||||||
| Brief Psychotic Disorder with Marked Stressors | 1/86 (1.2%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
| Parasomnia | 1/86 (1.2%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
| Reproductive system and breast disorders | ||||||||||||||||||||||||||||
| Endometriosis | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 1/67 (1.5%) | 0/152 (0%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||||||
| Angioedema | 1/86 (1.2%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
| Skin Exfoliation | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 1/186 (0.5%) | 0/89 (0%) | ||||||||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||||||||||
| Part 1 - 20 mg/Day | Part 1 - 40 mg/Day | Part 2 - 20 mg/Day Active | Part 2 - 40 mg/Day Active | Part 2 - 20 mg/Day Placebo | Part 2 - 40 mg/Day Placebo | Part 3 - Stay on Active 20 mg/Day | Part 3 - Stay on Active 40 mg/Day | Part 3 - Switch From Placebo to Active 20 mg/Day | Part 3 - Switch From Placebo to Active 40 mg/Day | Part 4 - < 20 mg/Day | Part 4 - 20 to < 40 mg/Day | Part 4 - 40 to < 60 mg/Day | Part 4 - >= 60 mg/Day | |||||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 70/86 (81.4%) | 59/78 (75.6%) | 27/34 (79.4%) | 28/32 (87.5%) | 14/15 (93.3%) | 13/14 (92.9%) | 19/23 (82.6%) | 15/18 (83.3%) | 8/11 (72.7%) | 7/8 (87.5%) | 62/67 (92.5%) | 105/152 (69.1%) | 178/186 (95.7%) | 59/89 (66.3%) | ||||||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||||||||
| Lymphadenopathy | 0/86 (0%) | 5/78 (6.4%) | 1/34 (2.9%) | 0/32 (0%) | 0/15 (0%) | 2/14 (14.3%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 1/8 (12.5%) | 1/67 (1.5%) | 8/152 (5.3%) | 18/186 (9.7%) | 3/89 (3.4%) | ||||||||||||||
| Ear and labyrinth disorders | ||||||||||||||||||||||||||||
| Ear pain | 0/86 (0%) | 1/78 (1.3%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 1/14 (7.1%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 1/67 (1.5%) | 3/152 (2%) | 4/186 (2.2%) | 2/89 (2.2%) | ||||||||||||||
| Tinnitus | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 1/15 (6.7%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 1/186 (0.5%) | 0/89 (0%) | ||||||||||||||
| Vertigo | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 1/14 (7.1%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 3/67 (4.5%) | 1/152 (0.7%) | 3/186 (1.6%) | 0/89 (0%) | ||||||||||||||
| Eye disorders | ||||||||||||||||||||||||||||
| Blepharospasm | 0/86 (0%) | 1/78 (1.3%) | 0/34 (0%) | 0/32 (0%) | 1/15 (6.7%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||||||||||
| Vomiting | 4/86 (4.7%) | 2/78 (2.6%) | 1/34 (2.9%) | 1/32 (3.1%) | 0/15 (0%) | 1/14 (7.1%) | 1/23 (4.3%) | 1/18 (5.6%) | 1/11 (9.1%) | 1/8 (12.5%) | 8/67 (11.9%) | 18/152 (11.8%) | 34/186 (18.3%) | 13/89 (14.6%) | ||||||||||||||
| Nausea | 5/86 (5.8%) | 5/78 (6.4%) | 4/34 (11.8%) | 1/32 (3.1%) | 1/15 (6.7%) | 1/14 (7.1%) | 0/23 (0%) | 3/18 (16.7%) | 0/11 (0%) | 0/8 (0%) | 10/67 (14.9%) | 11/152 (7.2%) | 28/186 (15.1%) | 16/89 (18%) | ||||||||||||||
| Diarrhoea | 4/86 (4.7%) | 5/78 (6.4%) | 2/34 (5.9%) | 2/32 (6.3%) | 0/15 (0%) | 0/14 (0%) | 1/23 (4.3%) | 0/18 (0%) | 1/11 (9.1%) | 0/8 (0%) | 8/67 (11.9%) | 15/152 (9.9%) | 25/186 (13.4%) | 9/89 (10.1%) | ||||||||||||||
| Abdominal pain upper | 1/86 (1.2%) | 0/78 (0%) | 1/34 (2.9%) | 1/32 (3.1%) | 0/15 (0%) | 1/14 (7.1%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 7/67 (10.4%) | 5/152 (3.3%) | 17/186 (9.1%) | 4/89 (4.5%) | ||||||||||||||
| Dyspepsia | 3/86 (3.5%) | 3/78 (3.8%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 1/23 (4.3%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 3/67 (4.5%) | 10/152 (6.6%) | 10/186 (5.4%) | 5/89 (5.6%) | ||||||||||||||
| Abdominal pain | 1/86 (1.2%) | 2/78 (2.6%) | 2/34 (5.9%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 1/18 (5.6%) | 0/11 (0%) | 0/8 (0%) | 4/67 (6%) | 7/152 (4.6%) | 10/186 (5.4%) | 6/89 (6.7%) | ||||||||||||||
| Toothache | 1/86 (1.2%) | 2/78 (2.6%) | 1/34 (2.9%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 1/23 (4.3%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 4/67 (6%) | 6/152 (3.9%) | 12/186 (6.5%) | 5/89 (5.6%) | ||||||||||||||
| Gastrooesophageal reflux disease | 1/86 (1.2%) | 2/78 (2.6%) | 0/34 (0%) | 2/32 (6.3%) | 1/15 (6.7%) | 1/14 (7.1%) | 0/23 (0%) | 1/18 (5.6%) | 0/11 (0%) | 0/8 (0%) | 3/67 (4.5%) | 6/152 (3.9%) | 8/186 (4.3%) | 9/89 (10.1%) | ||||||||||||||
| Constipation | 1/86 (1.2%) | 1/78 (1.3%) | 0/34 (0%) | 0/32 (0%) | 1/15 (6.7%) | 1/14 (7.1%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 2/67 (3%) | 3/152 (2%) | 10/186 (5.4%) | 6/89 (6.7%) | ||||||||||||||
| Abdominal discomfort | 2/86 (2.3%) | 0/78 (0%) | 1/34 (2.9%) | 0/32 (0%) | 1/15 (6.7%) | 0/14 (0%) | 0/23 (0%) | 1/18 (5.6%) | 0/11 (0%) | 0/8 (0%) | 1/67 (1.5%) | 3/152 (2%) | 11/186 (5.9%) | 2/89 (2.2%) | ||||||||||||||
| Frequent bowel movements | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 1/18 (5.6%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
| Abdominal distension | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 1/152 (0.7%) | 2/186 (1.1%) | 5/89 (5.6%) | ||||||||||||||
| General disorders | ||||||||||||||||||||||||||||
| Injection site reaction | 13/86 (15.1%) | 7/78 (9%) | 4/34 (11.8%) | 1/32 (3.1%) | 1/15 (6.7%) | 1/14 (7.1%) | 3/23 (13%) | 1/18 (5.6%) | 1/11 (9.1%) | 0/8 (0%) | 6/67 (9%) | 14/152 (9.2%) | 46/186 (24.7%) | 11/89 (12.4%) | ||||||||||||||
| Injection site bruising | 9/86 (10.5%) | 7/78 (9%) | 2/34 (5.9%) | 1/32 (3.1%) | 2/15 (13.3%) | 1/14 (7.1%) | 2/23 (8.7%) | 1/18 (5.6%) | 0/11 (0%) | 0/8 (0%) | 5/67 (7.5%) | 14/152 (9.2%) | 41/186 (22%) | 12/89 (13.5%) | ||||||||||||||
| Injection site pruritus | 6/86 (7%) | 3/78 (3.8%) | 1/34 (2.9%) | 1/32 (3.1%) | 0/15 (0%) | 0/14 (0%) | 1/23 (4.3%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 3/67 (4.5%) | 9/152 (5.9%) | 24/186 (12.9%) | 10/89 (11.2%) | ||||||||||||||
| Fatigue | 8/86 (9.3%) | 3/78 (3.8%) | 4/34 (11.8%) | 3/32 (9.4%) | 3/15 (20%) | 0/14 (0%) | 5/23 (21.7%) | 4/18 (22.2%) | 0/11 (0%) | 1/8 (12.5%) | 10/67 (14.9%) | 8/152 (5.3%) | 14/186 (7.5%) | 10/89 (11.2%) | ||||||||||||||
| Injection site induration | 2/86 (2.3%) | 0/78 (0%) | 0/34 (0%) | 1/32 (3.1%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 1/18 (5.6%) | 0/11 (0%) | 0/8 (0%) | 4/67 (6%) | 14/152 (9.2%) | 24/186 (12.9%) | 6/89 (6.7%) | ||||||||||||||
| Injection site pain | 3/86 (3.5%) | 0/78 (0%) | 1/34 (2.9%) | 1/32 (3.1%) | 1/15 (6.7%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 3/67 (4.5%) | 10/152 (6.6%) | 22/186 (11.8%) | 9/89 (10.1%) | ||||||||||||||
| Injection site swelling | 5/86 (5.8%) | 2/78 (2.6%) | 2/34 (5.9%) | 0/32 (0%) | 0/15 (0%) | 1/14 (7.1%) | 1/23 (4.3%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 4/67 (6%) | 9/152 (5.9%) | 19/186 (10.2%) | 3/89 (3.4%) | ||||||||||||||
| Injection site erythema | 4/86 (4.7%) | 5/78 (6.4%) | 2/34 (5.9%) | 2/32 (6.3%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 1/8 (12.5%) | 3/67 (4.5%) | 3/152 (2%) | 19/186 (10.2%) | 7/89 (7.9%) | ||||||||||||||
| Pyrexia | 2/86 (2.3%) | 1/78 (1.3%) | 0/34 (0%) | 1/32 (3.1%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 4/67 (6%) | 4/152 (2.6%) | 19/186 (10.2%) | 6/89 (6.7%) | ||||||||||||||
| Peripheral swelling | 2/86 (2.3%) | 1/78 (1.3%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 3/67 (4.5%) | 4/152 (2.6%) | 15/186 (8.1%) | 2/89 (2.2%) | ||||||||||||||
| Pain | 2/86 (2.3%) | 2/78 (2.6%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 2/18 (11.1%) | 0/11 (0%) | 0/8 (0%) | 5/67 (7.5%) | 2/152 (1.3%) | 10/186 (5.4%) | 5/89 (5.6%) | ||||||||||||||
| Injection site mass | 0/86 (0%) | 3/78 (3.8%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 2/152 (1.3%) | 12/186 (6.5%) | 0/89 (0%) | ||||||||||||||
| Non-cardiac chest pain | 2/86 (2.3%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 4/152 (2.6%) | 10/186 (5.4%) | 1/89 (1.1%) | ||||||||||||||
| Injection site haemorrhage | 1/86 (1.2%) | 1/78 (1.3%) | 1/34 (2.9%) | 2/32 (6.3%) | 0/15 (0%) | 0/14 (0%) | 1/23 (4.3%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 3/67 (4.5%) | 5/152 (3.3%) | 5/186 (2.7%) | 5/89 (5.6%) | ||||||||||||||
| Chest discomfort | 1/86 (1.2%) | 0/78 (0%) | 2/34 (5.9%) | 0/32 (0%) | 0/15 (0%) | 1/14 (7.1%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 1/152 (0.7%) | 2/186 (1.1%) | 1/89 (1.1%) | ||||||||||||||
| Feeling abnormal | 1/86 (1.2%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 1/15 (6.7%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 2/186 (1.1%) | 2/89 (2.2%) | ||||||||||||||
| Inflammation | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 1/15 (6.7%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 1/67 (1.5%) | 1/152 (0.7%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
| Chest pain | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 1/32 (3.1%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 1/11 (9.1%) | 0/8 (0%) | 1/67 (1.5%) | 1/152 (0.7%) | 6/186 (3.2%) | 0/89 (0%) | ||||||||||||||
| Malaise | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 1/11 (9.1%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
| Immune system disorders | ||||||||||||||||||||||||||||
| Seasonal allergy | 2/86 (2.3%) | 2/78 (2.6%) | 0/34 (0%) | 2/32 (6.3%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 1/18 (5.6%) | 1/11 (9.1%) | 0/8 (0%) | 8/67 (11.9%) | 6/152 (3.9%) | 19/186 (10.2%) | 3/89 (3.4%) | ||||||||||||||
| Hypersensitivity | 0/86 (0%) | 2/78 (2.6%) | 1/34 (2.9%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 1/23 (4.3%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 1/67 (1.5%) | 3/152 (2%) | 10/186 (5.4%) | 2/89 (2.2%) | ||||||||||||||
| Infections and infestations | ||||||||||||||||||||||||||||
| Nasopharyngitis | 7/86 (8.1%) | 11/78 (14.1%) | 4/34 (11.8%) | 1/32 (3.1%) | 0/15 (0%) | 1/14 (7.1%) | 2/23 (8.7%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 15/67 (22.4%) | 27/152 (17.8%) | 59/186 (31.7%) | 19/89 (21.3%) | ||||||||||||||
| Upper respiratory tract infection | 8/86 (9.3%) | 5/78 (6.4%) | 1/34 (2.9%) | 0/32 (0%) | 3/15 (20%) | 2/14 (14.3%) | 3/23 (13%) | 2/18 (11.1%) | 1/11 (9.1%) | 0/8 (0%) | 14/67 (20.9%) | 29/152 (19.1%) | 51/186 (27.4%) | 10/89 (11.2%) | ||||||||||||||
| Sinusitis | 1/86 (1.2%) | 2/78 (2.6%) | 1/34 (2.9%) | 1/32 (3.1%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 1/18 (5.6%) | 1/11 (9.1%) | 1/8 (12.5%) | 9/67 (13.4%) | 13/152 (8.6%) | 22/186 (11.8%) | 11/89 (12.4%) | ||||||||||||||
| Influenza | 1/86 (1.2%) | 0/78 (0%) | 1/34 (2.9%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 1/18 (5.6%) | 0/11 (0%) | 0/8 (0%) | 3/67 (4.5%) | 5/152 (3.3%) | 15/186 (8.1%) | 8/89 (9%) | ||||||||||||||
| Bronchitis | 1/86 (1.2%) | 0/78 (0%) | 1/34 (2.9%) | 1/32 (3.1%) | 1/15 (6.7%) | 1/14 (7.1%) | 0/23 (0%) | 1/18 (5.6%) | 1/11 (9.1%) | 0/8 (0%) | 3/67 (4.5%) | 9/152 (5.9%) | 13/186 (7%) | 3/89 (3.4%) | ||||||||||||||
| Gastroenteritis viral | 1/86 (1.2%) | 1/78 (1.3%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 5/67 (7.5%) | 7/152 (4.6%) | 11/186 (5.9%) | 7/89 (7.9%) | ||||||||||||||
| Urinary tract infection | 1/86 (1.2%) | 3/78 (3.8%) | 2/34 (5.9%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 1/18 (5.6%) | 0/11 (0%) | 0/8 (0%) | 3/67 (4.5%) | 5/152 (3.3%) | 13/186 (7%) | 3/89 (3.4%) | ||||||||||||||
| Pharyngitis streptococcal | 0/86 (0%) | 2/78 (2.6%) | 0/34 (0%) | 1/32 (3.1%) | 0/15 (0%) | 1/14 (7.1%) | 0/23 (0%) | 1/18 (5.6%) | 1/11 (9.1%) | 0/8 (0%) | 3/67 (4.5%) | 1/152 (0.7%) | 10/186 (5.4%) | 4/89 (4.5%) | ||||||||||||||
| Ear infection | 0/86 (0%) | 3/78 (3.8%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 1/14 (7.1%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 3/67 (4.5%) | 4/152 (2.6%) | 6/186 (3.2%) | 3/89 (3.4%) | ||||||||||||||
| Viral infection | 1/86 (1.2%) | 0/78 (0%) | 0/34 (0%) | 1/32 (3.1%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 2/67 (3%) | 3/152 (2%) | 10/186 (5.4%) | 1/89 (1.1%) | ||||||||||||||
| Gastroenteritis | 0/86 (0%) | 1/78 (1.3%) | 0/34 (0%) | 1/32 (3.1%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 4/67 (6%) | 2/152 (1.3%) | 6/186 (3.2%) | 2/89 (2.2%) | ||||||||||||||
| Conjunctivitis | 0/86 (0%) | 1/78 (1.3%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 1/14 (7.1%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 1/67 (1.5%) | 4/152 (2.6%) | 6/186 (3.2%) | 1/89 (1.1%) | ||||||||||||||
| Fungal infection | 0/86 (0%) | 1/78 (1.3%) | 1/34 (2.9%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 1/18 (5.6%) | 0/11 (0%) | 0/8 (0%) | 1/67 (1.5%) | 3/152 (2%) | 2/186 (1.1%) | 3/89 (3.4%) | ||||||||||||||
| Fungal skin infection | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 1/15 (6.7%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 1/186 (0.5%) | 0/89 (0%) | ||||||||||||||
| Laryngitis | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 1/15 (6.7%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 1/152 (0.7%) | 3/186 (1.6%) | 0/89 (0%) | ||||||||||||||
| Labyrinthitis | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 1/8 (12.5%) | 2/67 (3%) | 0/152 (0%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
| Vaginal infection | 1/86 (1.2%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 1/11 (9.1%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 1/186 (0.5%) | 0/89 (0%) | ||||||||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||||||||||||
| Contusion | 3/86 (3.5%) | 3/78 (3.8%) | 1/34 (2.9%) | 1/32 (3.1%) | 2/15 (13.3%) | 0/14 (0%) | 1/23 (4.3%) | 0/18 (0%) | 2/11 (18.2%) | 1/8 (12.5%) | 9/67 (13.4%) | 9/152 (5.9%) | 22/186 (11.8%) | 5/89 (5.6%) | ||||||||||||||
| Arthropod bite | 0/86 (0%) | 1/78 (1.3%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 1/23 (4.3%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 1/67 (1.5%) | 3/152 (2%) | 12/186 (6.5%) | 4/89 (4.5%) | ||||||||||||||
| Ligament sprain | 0/86 (0%) | 1/78 (1.3%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 2/67 (3%) | 5/152 (3.3%) | 7/186 (3.8%) | 5/89 (5.6%) | ||||||||||||||
| Muscle strain | 1/86 (1.2%) | 0/78 (0%) | 1/34 (2.9%) | 0/32 (0%) | 0/15 (0%) | 1/14 (7.1%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 2/67 (3%) | 2/152 (1.3%) | 8/186 (4.3%) | 2/89 (2.2%) | ||||||||||||||
| Post-traumatic pain | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 1/15 (6.7%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
| Road traffic accident | 0/86 (0%) | 1/78 (1.3%) | 0/34 (0%) | 0/32 (0%) | 1/15 (6.7%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 2/67 (3%) | 2/152 (1.3%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
| Skin abrasion | 2/86 (2.3%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 1/14 (7.1%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 1/67 (1.5%) | 1/152 (0.7%) | 2/186 (1.1%) | 1/89 (1.1%) | ||||||||||||||
| Injury | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 1/18 (5.6%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 1/186 (0.5%) | 0/89 (0%) | ||||||||||||||
| Investigations | ||||||||||||||||||||||||||||
| Amino acid level decreased | 3/86 (3.5%) | 1/78 (1.3%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 1/18 (5.6%) | 0/11 (0%) | 0/8 (0%) | 9/67 (13.4%) | 13/152 (8.6%) | 37/186 (19.9%) | 13/89 (14.6%) | ||||||||||||||
| Blood creatine phosphokinase increased | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 1/32 (3.1%) | 2/15 (13.3%) | 1/14 (7.1%) | 1/23 (4.3%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 1/67 (1.5%) | 0/152 (0%) | 6/186 (3.2%) | 1/89 (1.1%) | ||||||||||||||
| Complement factor C3 decreased | 1/86 (1.2%) | 2/78 (2.6%) | 2/34 (5.9%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 1/23 (4.3%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 1/67 (1.5%) | 1/152 (0.7%) | 5/186 (2.7%) | 0/89 (0%) | ||||||||||||||
| Blood bilirubin increased | 1/86 (1.2%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 1/15 (6.7%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 1/186 (0.5%) | 0/89 (0%) | ||||||||||||||
| Weight decreased | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 1/14 (7.1%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 1/186 (0.5%) | 0/89 (0%) | ||||||||||||||
| Weight increased | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 1/15 (6.7%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 1/152 (0.7%) | 1/186 (0.5%) | 0/89 (0%) | ||||||||||||||
| Blood cortisol decreased | 0/86 (0%) | 1/78 (1.3%) | 0/34 (0%) | 1/32 (3.1%) | 0/15 (0%) | 0/14 (0%) | 1/23 (4.3%) | 1/18 (5.6%) | 0/11 (0%) | 0/8 (0%) | 3/67 (4.5%) | 0/152 (0%) | 2/186 (1.1%) | 1/89 (1.1%) | ||||||||||||||
| Complement factor decreased | 1/86 (1.2%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 1/8 (12.5%) | 0/67 (0%) | 0/152 (0%) | 1/186 (0.5%) | 1/89 (1.1%) | ||||||||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||||||||||||
| Hypoglycaemia | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 1/14 (7.1%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 1/152 (0.7%) | 2/186 (1.1%) | 0/89 (0%) | ||||||||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||||||
| Arthralgia | 9/86 (10.5%) | 13/78 (16.7%) | 7/34 (20.6%) | 2/32 (6.3%) | 1/15 (6.7%) | 2/14 (14.3%) | 3/23 (13%) | 0/18 (0%) | 3/11 (27.3%) | 2/8 (25%) | 16/67 (23.9%) | 33/152 (21.7%) | 64/186 (34.4%) | 22/89 (24.7%) | ||||||||||||||
| Back pain | 4/86 (4.7%) | 0/78 (0%) | 0/34 (0%) | 1/32 (3.1%) | 1/15 (6.7%) | 1/14 (7.1%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 10/67 (14.9%) | 14/152 (9.2%) | 33/186 (17.7%) | 7/89 (7.9%) | ||||||||||||||
| Pain in extremity | 5/86 (5.8%) | 4/78 (5.1%) | 1/34 (2.9%) | 1/32 (3.1%) | 0/15 (0%) | 1/14 (7.1%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 9/67 (13.4%) | 14/152 (9.2%) | 24/186 (12.9%) | 10/89 (11.2%) | ||||||||||||||
| Musculoskeletal pain | 3/86 (3.5%) | 3/78 (3.8%) | 1/34 (2.9%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 4/67 (6%) | 6/152 (3.9%) | 16/186 (8.6%) | 3/89 (3.4%) | ||||||||||||||
| Myalgia | 2/86 (2.3%) | 3/78 (3.8%) | 0/34 (0%) | 2/32 (6.3%) | 1/15 (6.7%) | 0/14 (0%) | 0/23 (0%) | 1/18 (5.6%) | 1/11 (9.1%) | 0/8 (0%) | 4/67 (6%) | 5/152 (3.3%) | 15/186 (8.1%) | 2/89 (2.2%) | ||||||||||||||
| Neck pain | 0/86 (0%) | 2/78 (2.6%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 5/67 (7.5%) | 1/152 (0.7%) | 12/186 (6.5%) | 5/89 (5.6%) | ||||||||||||||
| Muscle spasms | 1/86 (1.2%) | 2/78 (2.6%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 3/67 (4.5%) | 3/152 (2%) | 8/186 (4.3%) | 5/89 (5.6%) | ||||||||||||||
| Flank pain | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 1/18 (5.6%) | 0/11 (0%) | 0/8 (0%) | 1/67 (1.5%) | 0/152 (0%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
| Nervous system disorders | ||||||||||||||||||||||||||||
| Headache | 16/86 (18.6%) | 12/78 (15.4%) | 6/34 (17.6%) | 2/32 (6.3%) | 3/15 (20%) | 4/14 (28.6%) | 2/23 (8.7%) | 3/18 (16.7%) | 1/11 (9.1%) | 0/8 (0%) | 20/67 (29.9%) | 29/152 (19.1%) | 59/186 (31.7%) | 24/89 (27%) | ||||||||||||||
| Dizziness | 2/86 (2.3%) | 7/78 (9%) | 1/34 (2.9%) | 2/32 (6.3%) | 1/15 (6.7%) | 0/14 (0%) | 0/23 (0%) | 1/18 (5.6%) | 0/11 (0%) | 0/8 (0%) | 10/67 (14.9%) | 6/152 (3.9%) | 21/186 (11.3%) | 11/89 (12.4%) | ||||||||||||||
| Migraine | 3/86 (3.5%) | 2/78 (2.6%) | 0/34 (0%) | 2/32 (6.3%) | 1/15 (6.7%) | 0/14 (0%) | 1/23 (4.3%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 6/67 (9%) | 8/152 (5.3%) | 18/186 (9.7%) | 9/89 (10.1%) | ||||||||||||||
| Disturbance in attention | 0/86 (0%) | 0/78 (0%) | 4/34 (11.8%) | 1/32 (3.1%) | 2/15 (13.3%) | 0/14 (0%) | 1/23 (4.3%) | 0/18 (0%) | 0/11 (0%) | 1/8 (12.5%) | 1/67 (1.5%) | 3/152 (2%) | 5/186 (2.7%) | 3/89 (3.4%) | ||||||||||||||
| Lethargy | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 2/15 (13.3%) | 0/14 (0%) | 0/23 (0%) | 1/18 (5.6%) | 1/11 (9.1%) | 1/8 (12.5%) | 1/67 (1.5%) | 1/152 (0.7%) | 8/186 (4.3%) | 1/89 (1.1%) | ||||||||||||||
| Memory impairment | 0/86 (0%) | 2/78 (2.6%) | 3/34 (8.8%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 2/67 (3%) | 0/152 (0%) | 4/186 (2.2%) | 1/89 (1.1%) | ||||||||||||||
| Tremor | 1/86 (1.2%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 1/15 (6.7%) | 1/14 (7.1%) | 0/23 (0%) | 1/18 (5.6%) | 0/11 (0%) | 0/8 (0%) | 4/67 (6%) | 0/152 (0%) | 4/186 (2.2%) | 2/89 (2.2%) | ||||||||||||||
| Dyspraxia | 0/86 (0%) | 0/78 (0%) | 1/34 (2.9%) | 0/32 (0%) | 0/15 (0%) | 1/14 (7.1%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 0/186 (0%) | 1/89 (1.1%) | ||||||||||||||
| Sciatica | 0/86 (0%) | 0/78 (0%) | 1/34 (2.9%) | 0/32 (0%) | 0/15 (0%) | 1/14 (7.1%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 1/67 (1.5%) | 1/152 (0.7%) | 1/186 (0.5%) | 0/89 (0%) | ||||||||||||||
| Hyperreflexia | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 1/15 (6.7%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 2/67 (3%) | 0/152 (0%) | 4/186 (2.2%) | 0/89 (0%) | ||||||||||||||
| Paraesthesia | 1/86 (1.2%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 1/15 (6.7%) | 0/14 (0%) | 1/23 (4.3%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 1/67 (1.5%) | 2/152 (1.3%) | 5/186 (2.7%) | 2/89 (2.2%) | ||||||||||||||
| Somnolence | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 1/15 (6.7%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 1/186 (0.5%) | 0/89 (0%) | ||||||||||||||
| Presyncope | 1/86 (1.2%) | 0/78 (0%) | 1/34 (2.9%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 1/18 (5.6%) | 0/11 (0%) | 0/8 (0%) | 1/67 (1.5%) | 0/152 (0%) | 0/186 (0%) | 1/89 (1.1%) | ||||||||||||||
| Psychiatric disorders | ||||||||||||||||||||||||||||
| Anxiety | 2/86 (2.3%) | 2/78 (2.6%) | 4/34 (11.8%) | 3/32 (9.4%) | 0/15 (0%) | 2/14 (14.3%) | 1/23 (4.3%) | 1/18 (5.6%) | 1/11 (9.1%) | 0/8 (0%) | 11/67 (16.4%) | 10/152 (6.6%) | 23/186 (12.4%) | 6/89 (6.7%) | ||||||||||||||
| Depression | 0/86 (0%) | 1/78 (1.3%) | 1/34 (2.9%) | 2/32 (6.3%) | 2/15 (13.3%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 1/8 (12.5%) | 9/67 (13.4%) | 11/152 (7.2%) | 13/186 (7%) | 3/89 (3.4%) | ||||||||||||||
| Insomnia | 1/86 (1.2%) | 1/78 (1.3%) | 1/34 (2.9%) | 3/32 (9.4%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 6/67 (9%) | 7/152 (4.6%) | 17/186 (9.1%) | 2/89 (2.2%) | ||||||||||||||
| Irritability | 1/86 (1.2%) | 0/78 (0%) | 0/34 (0%) | 2/32 (6.3%) | 2/15 (13.3%) | 1/14 (7.1%) | 1/23 (4.3%) | 1/18 (5.6%) | 0/11 (0%) | 0/8 (0%) | 2/67 (3%) | 1/152 (0.7%) | 2/186 (1.1%) | 1/89 (1.1%) | ||||||||||||||
| Agitation | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 3/32 (9.4%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 1/186 (0.5%) | 0/89 (0%) | ||||||||||||||
| Depressive symptom | 1/86 (1.2%) | 0/78 (0%) | 2/34 (5.9%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 1/67 (1.5%) | 0/152 (0%) | 1/186 (0.5%) | 2/89 (2.2%) | ||||||||||||||
| Mood altered | 1/86 (1.2%) | 0/78 (0%) | 0/34 (0%) | 1/32 (3.1%) | 0/15 (0%) | 2/14 (14.3%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 1/186 (0.5%) | 2/89 (2.2%) | ||||||||||||||
| Distractibility | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 1/15 (6.7%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
| Emotional disorder | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 1/15 (6.7%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 1/152 (0.7%) | 1/186 (0.5%) | 1/89 (1.1%) | ||||||||||||||
| Stress | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 1/8 (12.5%) | 0/67 (0%) | 1/152 (0.7%) | 1/186 (0.5%) | 2/89 (2.2%) | ||||||||||||||
| Renal and urinary disorders | ||||||||||||||||||||||||||||
| Ketonuria | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 1/14 (7.1%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 2/186 (1.1%) | 0/89 (0%) | ||||||||||||||
| Proteinuria | 0/86 (0%) | 1/78 (1.3%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 1/14 (7.1%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 1/67 (1.5%) | 2/152 (1.3%) | 2/186 (1.1%) | 3/89 (3.4%) | ||||||||||||||
| Urine odour abnormal | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 1/15 (6.7%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 1/67 (1.5%) | 0/152 (0%) | 0/186 (0%) | 0/89 (0%) | ||||||||||||||
| Reproductive system and breast disorders | ||||||||||||||||||||||||||||
| Dysmenorrhoea | 5/86 (5.8%) | 1/78 (1.3%) | 3/34 (8.8%) | 0/32 (0%) | 0/15 (0%) | 1/14 (7.1%) | 2/23 (8.7%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 2/67 (3%) | 4/152 (2.6%) | 9/186 (4.8%) | 3/89 (3.4%) | ||||||||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||||||
| Cough | 6/86 (7%) | 2/78 (2.6%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 2/14 (14.3%) | 0/23 (0%) | 0/18 (0%) | 1/11 (9.1%) | 0/8 (0%) | 6/67 (9%) | 20/152 (13.2%) | 29/186 (15.6%) | 10/89 (11.2%) | ||||||||||||||
| Oropharyngeal pain | 4/86 (4.7%) | 6/78 (7.7%) | 1/34 (2.9%) | 1/32 (3.1%) | 0/15 (0%) | 1/14 (7.1%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 6/67 (9%) | 14/152 (9.2%) | 32/186 (17.2%) | 8/89 (9%) | ||||||||||||||
| Nasal congestion | 4/86 (4.7%) | 2/78 (2.6%) | 1/34 (2.9%) | 0/32 (0%) | 3/15 (20%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 1/11 (9.1%) | 0/8 (0%) | 9/67 (13.4%) | 12/152 (7.9%) | 20/186 (10.8%) | 8/89 (9%) | ||||||||||||||
| Sinus congestion | 3/86 (3.5%) | 2/78 (2.6%) | 2/34 (5.9%) | 1/32 (3.1%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 1/11 (9.1%) | 0/8 (0%) | 7/67 (10.4%) | 5/152 (3.3%) | 12/186 (6.5%) | 4/89 (4.5%) | ||||||||||||||
| Rhinorrhoea | 1/86 (1.2%) | 2/78 (2.6%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 1/14 (7.1%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 1/8 (12.5%) | 1/67 (1.5%) | 2/152 (1.3%) | 7/186 (3.8%) | 3/89 (3.4%) | ||||||||||||||
| Wheezing | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 1/18 (5.6%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 2/186 (1.1%) | 1/89 (1.1%) | ||||||||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||||||
| Rash | 2/86 (2.3%) | 6/78 (7.7%) | 2/34 (5.9%) | 3/32 (9.4%) | 1/15 (6.7%) | 0/14 (0%) | 2/23 (8.7%) | 2/18 (11.1%) | 0/11 (0%) | 1/8 (12.5%) | 7/67 (10.4%) | 8/152 (5.3%) | 34/186 (18.3%) | 14/89 (15.7%) | ||||||||||||||
| Pruritus | 2/86 (2.3%) | 7/78 (9%) | 1/34 (2.9%) | 4/32 (12.5%) | 0/15 (0%) | 1/14 (7.1%) | 1/23 (4.3%) | 1/18 (5.6%) | 1/11 (9.1%) | 0/8 (0%) | 6/67 (9%) | 13/152 (8.6%) | 33/186 (17.7%) | 14/89 (15.7%) | ||||||||||||||
| Urticaria | 4/86 (4.7%) | 0/78 (0%) | 2/34 (5.9%) | 1/32 (3.1%) | 0/15 (0%) | 0/14 (0%) | 1/23 (4.3%) | 1/18 (5.6%) | 0/11 (0%) | 1/8 (12.5%) | 4/67 (6%) | 12/152 (7.9%) | 28/186 (15.1%) | 12/89 (13.5%) | ||||||||||||||
| Alopecia | 2/86 (2.3%) | 4/78 (5.1%) | 2/34 (5.9%) | 0/32 (0%) | 2/15 (13.3%) | 1/14 (7.1%) | 0/23 (0%) | 1/18 (5.6%) | 0/11 (0%) | 0/8 (0%) | 5/67 (7.5%) | 12/152 (7.9%) | 12/186 (6.5%) | 6/89 (6.7%) | ||||||||||||||
| Erythema | 3/86 (3.5%) | 2/78 (2.6%) | 0/34 (0%) | 1/32 (3.1%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 0/8 (0%) | 5/67 (7.5%) | 6/152 (3.9%) | 9/186 (4.8%) | 4/89 (4.5%) | ||||||||||||||
| Pruritus generalised | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 1/11 (9.1%) | 0/8 (0%) | 2/67 (3%) | 2/152 (1.3%) | 8/186 (4.3%) | 4/89 (4.5%) | ||||||||||||||
| Dry skin | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 1/18 (5.6%) | 0/11 (0%) | 1/8 (12.5%) | 1/67 (1.5%) | 0/152 (0%) | 6/186 (3.2%) | 0/89 (0%) | ||||||||||||||
| Papule | 0/86 (0%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 0/11 (0%) | 1/8 (12.5%) | 0/67 (0%) | 2/152 (1.3%) | 4/186 (2.2%) | 0/89 (0%) | ||||||||||||||
| Rash maculo-papular | 1/86 (1.2%) | 0/78 (0%) | 0/34 (0%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 0/18 (0%) | 1/11 (9.1%) | 0/8 (0%) | 1/67 (1.5%) | 0/152 (0%) | 3/186 (1.6%) | 0/89 (0%) | ||||||||||||||
| Skin exfoliation | 0/86 (0%) | 0/78 (0%) | 1/34 (2.9%) | 0/32 (0%) | 0/15 (0%) | 0/14 (0%) | 0/23 (0%) | 1/18 (5.6%) | 0/11 (0%) | 0/8 (0%) | 0/67 (0%) | 0/152 (0%) | 1/186 (0.5%) | 0/89 (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 | Debra Lounsbury/Sr Principle Scientist, Clinical Sciences |
|---|---|
| Organization | BioMarin Pharmaceutical Inc |
| Phone | 415-506-6348 |
| Dlounsbury@bmrn.com |
Responsible Party:
BioMarin Pharmaceutical
ClinicalTrials.gov Identifier:
NCT01889862
Other Study ID Numbers:
- 165-302
First Posted:
Jul 1, 2013
Last Update Posted:
May 21, 2021
Last Verified:
Apr 1, 2021