Replagal Enzyme Replacement Therapy for Children With Fabry Disease
Sponsor
Shire (Industry)
Overall Status
Completed
CT.gov ID
NCT00084084
Collaborator
(none)
17
14
2
84.1
1.2
0
Study Details
Study Description
Brief Summary
Primary Objective(s):
-
To assess the safety of Replagal at a dose of 0.2 mg/kg administered over 40 (+/-10) minutes in children with Fabry disease
-
To assess the effect of Replagal on heart rate variability in patients 7 to 17 years of age
Secondary Objective(s):
-
To determine the pharmacokinetics of Replagal at baseline and after the initiation of enzyme replacement therapy (ERT)
-
To determine exploratory measurements of efficacy including renal function (ie, estimated glomerular filtration rate [eGFR] and creatinine clearance), clinical outcomes (in Cohorts 1 and 2), and sweating and left ventricular mass index (LVMI) (Cohort 1, Phase 1 only)
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
TKT029 is an open label multi-center study to assess the safety of enzyme replacement therapy with Replagal (agalsidase alfa) in children with Fabry disease, who have completed 6 months of agalsidase alfa therapy in study TKT023 (Cohort 1) or who are treatment-naïve (Cohort 2) and meet all inclusion/exclusion criteria of this study. The study will consist of every other week treatment with Replagal for 52 weeks, with periodic reassessments by Shire HGT for continuation of the study beyond 52 weeks. A decision on the part of the study sponsor to terminate the study may be made at any time.
In Cohort 1, safety and clinical measurement assessments performed during Week 25 or 26 of Study TKT023 served as the baseline assessments for TKT029. Patients in Cohort 1 began treatment with Replagal manufactured using a roller bottle process (Replagal RB); this portion of treatment is denoted as Cohort 1, Phase 1. Safety evaluation visits for Cohort 1, Phase 1 were to be performed at Weeks 13, 25, 55, and every 26 weeks thereafter until the patient discontinued from the study or transitioned to treatment with Replagal manufactured using a bioreactor process (Replagal AF). The transition to Replagal AF marked the restart of the study clock and was denoted as Cohort 1, Phase 2. Safety evaluation visits for Cohort 1, Phase 2 will be performed at Weeks 1, 13, 25, 55, and every 26 weeks thereafter until the patient discontinues from or the sponsor terminates the study.
Patients in Cohort 2 will receive treatment with Replagal AF only; therefore there is only 1 study phase for these patients. Screening assessments performed at Week -1 will serve as the baseline assessments for this study. Safety evaluation visits for Cohort 2 will be performed at Weeks 13, 25, 37, 55 and every 26 weeks thereafter until the patients discontinues from or the sponsor terminates the study.
The final study visit for both cohorts will follow 30 days after the study study drug infusion, at which time a final safety evaluation will be performed. Patients who complete the study will be interviewed by telephone 30 days after their last study infusion for resolution of any outstanding adverse events (AEs) or concomitant medication changes. Any patient who withdraws early from the study will have a final study visit 30 days after the last study drug infusion, at which time a final safety evaluation will be performed.
Study Design
Study Type:
Interventional
Actual Enrollment
:
17 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open Label Clinical Trial of Replagal Enzyme Replacement Therapy In Children With Fabry Disease Who Have Completed Study TKT023 or Who Are Naive to Enzyme Replacement Therapy
Actual Study Start Date
:
Jun 10, 2004
Actual Primary Completion Date
:
Jun 15, 2011
Actual Study Completion Date
:
Jun 15, 2011
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Agalsidase alfa (Cohort 1) Cohort 1: Patients who completed TKT023. |
Drug: Agalsidase alfa
0.2 mg/kg agalsidase alfa administered by IV infusion over 40 (+/- 10) minutes every other week for 52 weeks, with periodic reassessments for study continuation beyond 52 weeks
Other Names:
|
| Experimental: Agalsidase Alfa (Cohort 2) Cohort 2: Treatment-naive patients. |
Drug: Agalsidase alfa
0.2 mg/kg agalsidase alfa administered by IV infusion over 40 (+/- 10) minutes every other week for 52 weeks, with periodic reassessments for study continuation beyond 52 weeks
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Patients Who Experienced At Least One Adverse Event (AE) [362 weeks]
Secondary Outcome Measures
- Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 81 [Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.]
AUC0-∞ is a measure of the total exposure to a drug.
- Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 133 [Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.]
AUC0-∞ is a measure of the total exposure to a drug.
- Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 159 [Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.]
AUC0-∞ is a measure of the total exposure to a drug.
- Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 315/341 [Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.]
AUC0-∞ is a measure of the total exposure to a drug.
- Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) - Week 81 [Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.]
Cmax is the peak plasma concentration of a drug after administration.
- Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) - Week 133 [Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.]
Cmax is the peak plasma concentration of a drug after administration.
- Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) - Week 159 [Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.]
Cmax is the peak plasma concentration of a drug after administration.
- Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) - Week 315/341 [Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours.]
Cmax is the peak plasma concentration of a drug after administration.
Other Outcome Measures
- Heart Rate Variability - Change From Baseline at Week 185 in SDNN [Week 185]
Heart rate variability was assessed by 2-hour Holter monitoring. Standard deviation of all filtered RR intervals over the length of the analysis (SDNN) was measured.
Eligibility Criteria
Criteria
Ages Eligible for Study:
7 Years
to 17 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
1a. For Cohort 1 (both phases):
- Patients must have completed all study requirements and assessments for Study TKT023 less than 30 (+/-7) days prior to enrolling in Study TKT029 and must have no safety or medical issues that contraindicate participation.
OR
1b. For Cohort 2:
-
The patient is between 7 and 17 years of age at the time of informed consent, inclusive.
-
The patient must be ERT-naive.
-
The patient is a hemizygous male with Fabry disease as confirmed by a deficiency of alpha-galactosidase A activity measured in serum, leukocytes, or fibroblasts. Male patients who do not already have a documented deficiency of alpha-galactosidase A activity will provide a blood sample during screening for determination of alpha-galactosidase A activity level in their serum.
OR
- The patient is a heterozygous female or hemizygous male with Fabry disease as confirmed by a mutation of the alpha-galactosidase A gene. Patients who do not already have a documented mutation of the alpha-galactosidase A gene will provide a blood sample during screening for genotyping.
-
Adequate general health (as determined by the Investigators) to undergo the specified phlebotomy regimen and protocol-related procedures and no safety or medical contraindications for participation.
-
The minor child must assent to participate in the protocol and the parent(s) or legally authorized guardian(s) must have voluntarily signed an Institutional Review Board/Independent Ethics Committee (IRB/IEC) approved informed concent form after all relevant aspects of the study have been explained and discussed with the child and the child's parent(s) or legal guardian(s).
Exclusion Criteria:
Patients who meet any of the following criteria are not eligible for this study:
-
Patient and/or the patient's parent(s) or legal guardian(s) are unable to understand the nature, scope, and possible consequences of the study.
-
Patient is unable to comply with the protocol, e.g., uncooperative with protocol schedule, refusal to agree to all of the study procedures, inability to return for safety evaluations, or is otherwise unlikely to complete the study, as determined by the Investigator or the medical monitor.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Tucson Access Center of Arizona Kidney Disease Hypertension Center | Tucson | Arizona | United States | 85719 |
| 2 | University of Arizona Health Sciences Center | Tucson | Arizona | United States | 85724 |
| 3 | Children's Physician Group | Palm Beach Gardens | Florida | United States | 33410 |
| 4 | Christus St. Patrick Hospital | Lake Charles | Louisiana | United States | 70601 |
| 5 | Clinical Center, National Institutes of Health | Bethesda | Maryland | United States | 20892 |
| 6 | Memorial Hospital | Easton | Maryland | United States | 21601 |
| 7 | St. Louis Children's Hospital | Saint Louis | Missouri | United States | 63110 |
| 8 | NYU School of Medicine | New York | New York | United States | 10016 |
| 9 | Sacred Heart Hospital | Allentown | Pennsylvania | United States | 18102 |
| 10 | East Tennessee Children's Hospital | Knoxville | Tennessee | United States | 37916 |
| 11 | University of Tennessee, Health Science Center | Memphis | Tennessee | United States | 38163 |
| 12 | Institute of Metabolic Diseases | Dallas | Texas | United States | 75226 |
| 13 | Office of Michael Cohen | Stafford | Virginia | United States | 22556 |
| 14 | The Hospital for Sick Children | Toronto | Ontario | Canada | M5G 1X8 |
Sponsors and Collaborators
- Shire
Investigators
- Study Director: Study Director, Takeda
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Shire
ClinicalTrials.gov Identifier:
NCT00084084
Other Study ID Numbers:
- TKT029
First Posted:
Jun 7, 2004
Last Update Posted:
Jul 30, 2021
Last Verified:
Jul 1, 2021
Keywords provided by Shire
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | No patient was enrolled in Cohort 2 (ie, no treatment-naive patients were enrolled). |
| Arm/Group Title | Agalsidase Alfa (Cohort 1) |
|---|---|
| Arm/Group Description | Cohort 1 was composed of patients who had completed TKT023. Patients received 0.2 mg/kg agalsidase alfa, IV, every other week. |
| Period Title: Phase 1 (Treatment With Replagal RB) | |
| STARTED | 17 |
| COMPLETED | 16 |
| NOT COMPLETED | 1 |
| Period Title: Phase 1 (Treatment With Replagal RB) | |
| STARTED | 11 |
| COMPLETED | 10 |
| NOT COMPLETED | 1 |
Baseline Characteristics
| Arm/Group Title | Agalsidase Alfa (Cohort 1) |
|---|---|
| Arm/Group Description | 0.2 mg/kg agalsidase alfa infused by IV over 40 (+/- 10) minutes every other week |
| Overall Participants | 17 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
11.99
(3.2464)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
1
5.9%
|
| Male |
16
94.1%
|
| Race/Ethnicity, Customized (Count of Participants) | |
| White |
15
88.2%
|
| Hispanic |
2
11.8%
|
| Baseline Heart Rate Variability (SDNN) (msec) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [msec] |
98.947
(32.324)
|
Outcome Measures
| Title | Patients Who Experienced At Least One Adverse Event (AE) |
|---|---|
| Description | |
| Time Frame | 362 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population: Patients in Cohort 1 who received at least one dose of Replagal RB in Phase 1. |
| Arm/Group Title | Agalsidase Alfa (Cohort 1) |
|---|---|
| Arm/Group Description | Cohort 1 was composed of patients who had completed TKT023. Patients received 0.2 mg/kg agalsidase alfa, IV, every other week. |
| Measure Participants | 17 |
| Number [participants] |
17
100%
|
| Title | Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 81 |
|---|---|
| Description | AUC0-∞ is a measure of the total exposure to a drug. |
| Time Frame | Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours. |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Population: All patients who received at least 1 dose of Replagal (RB or AF) and had at least 1 PK sample drawn. |
| Arm/Group Title | Agalsidase Alfa (Cohort 1) |
|---|---|
| Arm/Group Description | Cohort 1 was composed of patients who had completed TKT023. Patients received 0.2 mg/kg agalsidase alfa, IV, every other week. |
| Measure Participants | 11 |
| Mean (Standard Deviation) [min·U/mL] |
245282
(159071)
|
| Title | Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 133 |
|---|---|
| Description | AUC0-∞ is a measure of the total exposure to a drug. |
| Time Frame | Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours. |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Population: All patients who received at least 1 dose of Replagal (RB or AF) and had at least 1 PK sample drawn. |
| Arm/Group Title | Agalsidase Alfa (Cohort 1) |
|---|---|
| Arm/Group Description | Cohort 1 was composed of patients who had completed TKT023. Patients received 0.2 mg/kg agalsidase alfa, IV, every other week. |
| Measure Participants | 11 |
| Mean (Standard Deviation) [min·U/mL] |
295779
(161058)
|
| Title | Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 159 |
|---|---|
| Description | AUC0-∞ is a measure of the total exposure to a drug. |
| Time Frame | Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours. |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Population: All patients who received at least 1 dose of Replagal (RB or AF) and had at least 1 PK sample drawn. |
| Arm/Group Title | Agalsidase Alfa (Cohort 1) |
|---|---|
| Arm/Group Description | Cohort 1 was composed of patients who had completed TKT023. Patients received 0.2 mg/kg agalsidase alfa, IV, every other week. |
| Measure Participants | 11 |
| Mean (Standard Deviation) [min·U/mL] |
218078
(73560)
|
| Title | Pharmacokinetics - Area Under the Serum Concentration-Time Curve (AUC0-∞) - Week 315/341 |
|---|---|
| Description | AUC0-∞ is a measure of the total exposure to a drug. |
| Time Frame | Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours. |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK Population: All patients who received at least 1 dose of Replagal (RB or AF) and had at least 1 PK sample drawn. |
| Arm/Group Title | Agalsidase Alfa (Cohort 1) |
|---|---|
| Arm/Group Description | Cohort 1 was composed of patients who had completed TKT023. Patients received 0.2 mg/kg agalsidase alfa, IV, every other week. |
| Measure Participants | 11 |
| Mean (Standard Deviation) [min·U/mL] |
213193
(119581)
|
| Title | Heart Rate Variability - Change From Baseline at Week 185 in SDNN |
|---|---|
| Description | Heart rate variability was assessed by 2-hour Holter monitoring. Standard deviation of all filtered RR intervals over the length of the analysis (SDNN) was measured. |
| Time Frame | Week 185 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of participants present at Visit Week 185 included for analysis. |
| Arm/Group Title | Agalsidase Alfa (Cohort 1) |
|---|---|
| Arm/Group Description | Cohort 1 was composed of patients who had completed TKT023. Patients received 0.2 mg/kg agalsidase alfa, IV, every other week. |
| Measure Participants | 9 |
| Mean (Standard Deviation) [msec] |
20.256
(29.060)
|
| Title | Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) - Week 81 |
|---|---|
| Description | Cmax is the peak plasma concentration of a drug after administration. |
| Time Frame | Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Agalsidase Alfa (Cohort 1) |
|---|---|
| Arm/Group Description | Cohort 1 was composed of patients who had completed TKT023. Patients received 0.2 mg/kg agalsidase alfa, IV, every other week. |
| Measure Participants | 11 |
| Mean (Standard Deviation) [U/mL] |
3173
(969)
|
| Title | Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) - Week 133 |
|---|---|
| Description | Cmax is the peak plasma concentration of a drug after administration. |
| Time Frame | Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Agalsidase Alfa (Cohort 1) |
|---|---|
| Arm/Group Description | Cohort 1 was composed of patients who had completed TKT023. Patients received 0.2 mg/kg agalsidase alfa, IV, every other week. |
| Measure Participants | 11 |
| Mean (Standard Deviation) [U/mL] |
3842
(1235)
|
| Title | Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) - Week 159 |
|---|---|
| Description | Cmax is the peak plasma concentration of a drug after administration. |
| Time Frame | Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Agalsidase Alfa (Cohort 1) |
|---|---|
| Arm/Group Description | Cohort 1 was composed of patients who had completed TKT023. Patients received 0.2 mg/kg agalsidase alfa, IV, every other week. |
| Measure Participants | 11 |
| Mean (Standard Deviation) [U/mL] |
3842
(1235)
|
| Title | Pharmacokinetics - Maximum Observed Serum Concentration (Cmax) - Week 315/341 |
|---|---|
| Description | Cmax is the peak plasma concentration of a drug after administration. |
| Time Frame | Pre-infusion; and post-infusion at 20, 40, 50, 60, 90 minutes, and 2, 3, 4, 8 hours. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Agalsidase Alfa (Cohort 1) |
|---|---|
| Arm/Group Description | Cohort 1 was composed of patients who had completed TKT023. Patients received 0.2 mg/kg agalsidase alfa, IV, every other week. |
| Measure Participants | 11 |
| Mean (Standard Deviation) [U/mL] |
3568
(1492)
|
Adverse Events
| Time Frame | 362 weeks | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Safety Population RB | Transition Safety Population | ||
| Arm/Group Description | Patients in Cohort 1 who received at least 1 dose of Replagal RB in Phase 1 - no data from Phase 2 (Replagal AF) included. | A subset of patients from the Safety Population RB who additionally received at least 1 dose of Replagal AF in Phase 2. | ||
All Cause Mortality |
||||
| Safety Population RB | Transition Safety Population | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Safety Population RB | Transition Safety Population | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/17 (11.8%) | 2/11 (18.2%) | ||
| Congenital, familial and genetic disorders | ||||
| Pectus Excavatum | 0/17 (0%) | 0 | 1/11 (9.1%) | 1 |
| Ear and labyrinth disorders | ||||
| Vertigo Positional | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Facial Bones Fracture | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Renal Injury | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Road Traffic Accident | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Traumatic Liver Injury | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Metabolism and nutrition disorders | ||||
| Dehydration | 1/17 (5.9%) | 1 | 0/11 (0%) | 0 |
| Nervous system disorders | ||||
| Neuralgia | 1/17 (5.9%) | 1 | 0/11 (0%) | 0 |
| Cerebrovascular Accident | 1/17 (5.9%) | 2 | 1/11 (9.1%) | 2 |
Other (Not Including Serious) Adverse Events |
||||
| Safety Population RB | Transition Safety Population | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 17/17 (100%) | 11/11 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 2/17 (11.8%) | 2 | 1/11 (9.1%) | 1 |
| Lymphadenopathy | 2/17 (11.8%) | 2 | 2/11 (18.2%) | 2 |
| Cardiac disorders | ||||
| Arrhythmia Supraventricular | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Atrioventricular Block First Degree | 1/17 (5.9%) | 1 | 0/11 (0%) | 0 |
| Palpitations | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Sinus Tachycardia | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Tachycardia | 1/17 (5.9%) | 1 | 2/11 (18.2%) | 3 |
| Pericardial Effusion | 0/17 (0%) | 0 | 1/11 (9.1%) | 1 |
| Congenital, familial and genetic disorders | ||||
| Pectus Excavatum | 0/17 (0%) | 0 | 1/11 (9.1%) | 2 |
| Ear and labyrinth disorders | ||||
| Ear Pain | 4/17 (23.5%) | 6 | 1/11 (9.1%) | 1 |
| Cerumen Impaction | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Deafness Unilateral | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Middle Ear Effusion | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Otorrhoea | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Tinnitus | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Tympanic Membrane Perforation | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Vertigo Positional | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Eye disorders | ||||
| Diplopia | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Eye Pain | 1/17 (5.9%) | 2 | 1/11 (9.1%) | 2 |
| Eye Swelling | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Gaze Palsy | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Myopia | 1/17 (5.9%) | 2 | 1/11 (9.1%) | 2 |
| Strabismus | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Refraction Disorder | 0/17 (0%) | 0 | 1/11 (9.1%) | 1 |
| Visual Acuity Reduced | 0/17 (0%) | 0 | 1/11 (9.1%) | 1 |
| Gastrointestinal disorders | ||||
| Abdominal Pain | 8/17 (47.1%) | 13 | 8/11 (72.7%) | 14 |
| Nausea | 7/17 (41.2%) | 11 | 5/11 (45.5%) | 15 |
| Abdominal Pain Upper | 6/17 (35.3%) | 10 | 6/11 (54.5%) | 12 |
| Vomiting | 6/17 (35.3%) | 13 | 6/11 (54.5%) | 12 |
| Diarrhoea | 4/17 (23.5%) | 11 | 6/11 (54.5%) | 17 |
| Abdominal Discomfort | 2/17 (11.8%) | 2 | 3/11 (27.3%) | 3 |
| Toothache | 2/17 (11.8%) | 2 | 2/11 (18.2%) | 2 |
| Aphthous Stomatitis | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Dental Caries | 1/17 (5.9%) | 1 | 0/11 (0%) | 0 |
| Faecal Incontinence | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Frequent Bowel Movements | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Gastritis | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Lip Swelling | 1/17 (5.9%) | 2 | 1/11 (9.1%) | 3 |
| Retching | 1/17 (5.9%) | 1 | 0/11 (0%) | 0 |
| Stomatitis | 1/17 (5.9%) | 1 | 2/11 (18.2%) | 2 |
| General disorders | ||||
| Pyrexia | 12/17 (70.6%) | 27 | 9/11 (81.8%) | 19 |
| Chest Pain | 6/17 (35.3%) | 9 | 7/11 (63.6%) | 13 |
| Fatigue | 4/17 (23.5%) | 5 | 4/11 (36.4%) | 6 |
| Pain | 3/17 (17.6%) | 5 | 4/11 (36.4%) | 8 |
| Gait Disturbance | 2/17 (11.8%) | 3 | 2/11 (18.2%) | 4 |
| Non-Cardiac Chest Pain | 2/17 (11.8%) | 2 | 5/11 (45.5%) | 7 |
| Oedema Peripheral | 2/17 (11.8%) | 2 | 2/11 (18.2%) | 3 |
| Asthenia | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Chest Discomfort | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Chills | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Infusion Site Pain | 1/17 (5.9%) | 1 | 0/11 (0%) | 0 |
| Irritability | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Temperature Intolerance | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Influenza Like Illness | 0/17 (0%) | 0 | 2/11 (18.2%) | 2 |
| Immune system disorders | ||||
| Drug Hypersensitivity | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Infections and infestations | ||||
| Gastroenteritis Viral | 8/17 (47.1%) | 12 | 5/11 (45.5%) | 6 |
| Nasopharyngitis | 7/17 (41.2%) | 12 | 6/11 (54.5%) | 12 |
| Upper Respiratory Tract Infection | 4/17 (23.5%) | 11 | 5/11 (45.5%) | 16 |
| Influenza | 3/17 (17.6%) | 3 | 3/11 (27.3%) | 3 |
| Bronchitis | 2/17 (11.8%) | 2 | 0/11 (0%) | 0 |
| Ear Infection | 2/17 (11.8%) | 3 | 2/11 (18.2%) | 3 |
| Sinusitis | 2/17 (11.8%) | 5 | 4/11 (36.4%) | 8 |
| Acarodermatitis | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Cellulitis | 1/17 (5.9%) | 2 | 1/11 (9.1%) | 2 |
| Hordeolum | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Impetigo | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Infected Bites | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Infectious Mononucleosis | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Lung Infection | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Otitis Media | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Pharyngitis Streptococcal | 1/17 (5.9%) | 2 | 1/11 (9.1%) | 2 |
| Pneumonia | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Rocky Mountain Spotted Fever | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Tinea Pedis | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Viral Infection | 1/17 (5.9%) | 1 | 3/11 (27.3%) | 3 |
| Gastroenteritis | 0/17 (0%) | 0 | 2/11 (18.2%) | 2 |
| Abscess | 0/17 (0%) | 0 | 1/11 (9.1%) | 1 |
| Blister Infected | 0/17 (0%) | 0 | 1/11 (9.1%) | 1 |
| Body Tinea | 0/17 (0%) | 0 | 1/11 (9.1%) | 1 |
| Localised Infection | 0/17 (0%) | 0 | 1/11 (9.1%) | 1 |
| Molluscum Contagiosum | 0/17 (0%) | 0 | 1/11 (9.1%) | 1 |
| Rhinitis | 0/17 (0%) | 0 | 1/11 (9.1%) | 1 |
| Tonsillitis | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Contusion | 5/17 (29.4%) | 15 | 5/11 (45.5%) | 16 |
| Excoriation | 5/17 (29.4%) | 16 | 5/11 (45.5%) | 16 |
| Post-Traumatic Pain | 4/17 (23.5%) | 5 | 4/11 (36.4%) | 5 |
| Fall | 3/17 (17.6%) | 8 | 3/11 (27.3%) | 8 |
| Skin Laceration | 3/17 (17.6%) | 9 | 3/11 (27.3%) | 10 |
| Joint Injury | 2/17 (11.8%) | 3 | 2/11 (18.2%) | 3 |
| Joint Sprain | 2/17 (11.8%) | 2 | 1/11 (9.1%) | 1 |
| Limb Injury | 2/17 (11.8%) | 4 | 2/11 (18.2%) | 4 |
| Procedural Pain | 2/17 (11.8%) | 2 | 4/11 (36.4%) | 4 |
| Arthropod Bite | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 3 |
| Facial Bones Fracture | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Head Injury | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Heat Exhaustion | 1/17 (5.9%) | 1 | 0/11 (0%) | 0 |
| Laceration | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Lumbar Vertebral Fracture | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Muscle Strain | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Renal Injury | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Road Traffic Accident | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Scratch | 1/17 (5.9%) | 1 | 2/11 (18.2%) | 2 |
| Thermal Burn | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Traumatic Haematoma | 1/17 (5.9%) | 2 | 1/11 (9.1%) | 2 |
| Traumatic Liver Injury | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Lower Limb Fracture | 0/17 (0%) | 0 | 1/11 (9.1%) | 1 |
| Neck Injury | 0/17 (0%) | 0 | 1/11 (9.1%) | 1 |
| Investigations | ||||
| Albumin Urine Present | 1/17 (5.9%) | 1 | 0/11 (0%) | 0 |
| Blood Albumin Increased | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Blood Pressure Increased | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Blood Triglycerides Increased | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| C-Reactive Protein Increased | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Nuclear Magnetic Resonance Imaging Brain Abnormal | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Pulmonary Function Test Decreased | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Sputum Abnormal | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Weight Decreased | 1/17 (5.9%) | 2 | 1/11 (9.1%) | 2 |
| Metabolism and nutrition disorders | ||||
| Decreased Appetite | 3/17 (17.6%) | 3 | 3/11 (27.3%) | 3 |
| Anorexia | 1/17 (5.9%) | 1 | 2/11 (18.2%) | 2 |
| Dehydration | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Obesity | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 8/17 (47.1%) | 9 | 5/11 (45.5%) | 9 |
| Pain in Extremity | 8/17 (47.1%) | 59 | 8/11 (72.7%) | 67 |
| Back Pain | 2/17 (11.8%) | 6 | 2/11 (18.2%) | 9 |
| Groin Pain | 2/17 (11.8%) | 2 | 2/11 (18.2%) | 2 |
| Muscular Weakness | 2/17 (11.8%) | 2 | 2/11 (18.2%) | 2 |
| Musculoskeletal Chest Pain | 2/17 (11.8%) | 3 | 3/11 (27.3%) | 4 |
| Myalgia | 2/17 (11.8%) | 2 | 2/11 (18.2%) | 2 |
| Neck Pain | 2/17 (11.8%) | 3 | 2/11 (18.2%) | 4 |
| Foot Deformity | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Limb Discomfort | 1/17 (5.9%) | 2 | 1/11 (9.1%) | 2 |
| Musculoskeletal Pain | 1/17 (5.9%) | 1 | 2/11 (18.2%) | 2 |
| Posture Abnormal | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Muscle Spasms | 0/17 (0%) | 0 | 1/11 (9.1%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Melanocytic Naevus | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Skin Papilloma | 0/17 (0%) | 0 | 1/11 (9.1%) | 1 |
| Nervous system disorders | ||||
| Headache | 9/17 (52.9%) | 33 | 7/11 (63.6%) | 46 |
| Neuralgia | 9/17 (52.9%) | 35 | 7/11 (63.6%) | 32 |
| Burning Sensation | 6/17 (35.3%) | 16 | 5/11 (45.5%) | 15 |
| Paraesthesia | 3/17 (17.6%) | 7 | 3/11 (27.3%) | 7 |
| Balance Disorder | 2/17 (11.8%) | 2 | 2/11 (18.2%) | 3 |
| Dizziness | 1/17 (5.9%) | 1 | 2/11 (18.2%) | 2 |
| Amnesia | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Cerebral Infarction | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Cerebrovascular Accident | 1/17 (5.9%) | 5 | 1/11 (9.1%) | 5 |
| Coordination Abnormal | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Cranial Nerve Disorder | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Dysarthria | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Facial Paresis | 1/17 (5.9%) | 3 | 1/11 (9.1%) | 3 |
| Hypersomnia | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Migraine | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Poor Quality Sleep | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Presyncope | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Reflexes Abnormal | 1/17 (5.9%) | 3 | 1/11 (9.1%) | 3 |
| Sinus Headache | 2/17 (11.8%) | 2 | 1/11 (9.1%) | 1 |
| Thalamic Infarction | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Tremor | 0/17 (0%) | 0 | 1/11 (9.1%) | 1 |
| Disturbance in Attention | 1/17 (5.9%) | 1 | 0/11 (0%) | 0 |
| Psychiatric disorders | ||||
| Attention Deficit / Hyperactivity Disorder | 3/17 (17.6%) | 4 | 2/11 (18.2%) | 3 |
| Anxiety | 1/17 (5.9%) | 2 | 1/11 (9.1%) | 2 |
| Decreased Activity | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Depression | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 3 |
| Panic Disorder | 1/17 (5.9%) | 2 | 1/11 (9.1%) | 2 |
| Agitation | 0/17 (0%) | 0 | 1/11 (9.1%) | 1 |
| Renal and urinary disorders | ||||
| Dysuria | 2/17 (11.8%) | 2 | 1/11 (9.1%) | 1 |
| Urethral Meatus Stenosis | 2/17 (11.8%) | 2 | 2/11 (18.2%) | 2 |
| Haematuria | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Nephrolithiasis | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Proteinuria | 0/17 (0%) | 0 | 1/11 (9.1%) | 1 |
| Reproductive system and breast disorders | ||||
| Testicular Pain | 2/17 (11.8%) | 2 | 2/11 (18.2%) | 2 |
| Balanitis | 1/17 (5.9%) | 2 | 1/11 (9.1%) | 2 |
| Scrotal Pain | 1/17 (5.9%) | 2 | 1/11 (9.1%) | 2 |
| Testicular Oedema | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Dysmenorrhoea | 0/17 (0%) | 0 | 1/11 (9.1%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 13/17 (76.5%) | 27 | 10/11 (90.9%) | 23 |
| Nasal Congestion | 10/17 (58.8%) | 16 | 6/11 (54.5%) | 14 |
| Oropharyngeal Pain | 5/17 (29.4%) | 8 | 5/11 (45.5%) | 14 |
| Rhinitis Allergic | 4/17 (23.5%) | 5 | 4/11 (36.4%) | 5 |
| Dyspnoea | 3/17 (17.6%) | 4 | 6/11 (54.5%) | 10 |
| Upper Respiratory Tract Congestion | 3/17 (17.6%) | 4 | 3/11 (27.3%) | 4 |
| Asthma | 2/17 (11.8%) | 2 | 2/11 (18.2%) | 2 |
| Sinus Congestion | 2/17 (11.8%) | 2 | 2/11 (18.2%) | 2 |
| Productive Cough | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Respiratory Tract Congestion | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 4 |
| Rhinorrhoea | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Pleural Effusion | 0/17 (0%) | 0 | 1/11 (9.1%) | 1 |
| Wheezing | 0/17 (0%) | 0 | 1/11 (9.1%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Dermatitis Contact | 3/17 (17.6%) | 5 | 3/11 (27.3%) | 6 |
| Erythema | 3/17 (17.6%) | 5 | 3/11 (27.3%) | 5 |
| Acne | 1/17 (5.9%) | 1 | 2/11 (18.2%) | 2 |
| Angiokeratoma | 1/17 (5.9%) | 2 | 3/11 (27.3%) | 4 |
| Ecchymosis | 1/17 (5.9%) | 3 | 1/11 (9.1%) | 3 |
| Eczema | 1/17 (5.9%) | 2 | 2/11 (18.2%) | 3 |
| Hyperhidrosis | 1/17 (5.9%) | 1 | 0/11 (0%) | 0 |
| Petechiae | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Pruritus | 1/17 (5.9%) | 2 | 1/11 (9.1%) | 2 |
| Pruritus Generalised | 1/17 (5.9%) | 2 | 1/11 (9.1%) | 2 |
| Rash | 1/17 (5.9%) | 3 | 3/11 (27.3%) | 5 |
| Rash Generalised | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Rash Papular | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Rash Pruritic | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Skin Lesion | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Urticaria | 1/17 (5.9%) | 5 | 1/11 (9.1%) | 6 |
| Vasculitic Rash | 1/17 (5.9%) | 3 | 0/11 (0%) | 0 |
| Angioedema | 0/17 (0%) | 0 | 1/11 (9.1%) | 1 |
| Vascular disorders | ||||
| Flushing | 2/17 (11.8%) | 2 | 2/11 (18.2%) | 6 |
| Haematoma | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Haemorrhage | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Hypertension | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
| Pallor | 1/17 (5.9%) | 1 | 1/11 (9.1%) | 1 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Shire's agreements with investigators vary. All agreements provide Shire the right to embargo communications regarding trial results prior to public release for a period ≤ 180 days from the time submitted to Shire for review. Shire does not prohibit publication but can require the removal of confidential information (excluding trial results) and can request postponement of a single-center publication until after disclosure of the trial's multi-center publication.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Shire |
| Phone | +1 866 842 5335 |
| ClinicalTransparency@shire.com |
Responsible Party:
Shire
ClinicalTrials.gov Identifier:
NCT00084084
Other Study ID Numbers:
- TKT029
First Posted:
Jun 7, 2004
Last Update Posted:
Jul 30, 2021
Last Verified:
Jul 1, 2021