Trial Outcomes & Findings for Extension of Study TKT024 Evaluating Long-Term Safety and Clinical Outcomes in MPS II Patients Receiving Idursulfase (NCT NCT00630747)

NCT ID: NCT00630747

Last Updated: 2021-06-10

Results Overview

Determined by spirometry. The change is calculated as Week 105 minus baseline.

• Recruitment status: COMPLETED
• Study phase: PHASE2/PHASE3
• Target enrollment: 94 participants
• Primary outcome timeframe: Baseline and at Week 105
• Results posted on: 2021-06-10

Participant Flow

This study allows participants in double-blind phase of Study TKT024 (NCT00069641), a 1 year Phase 2/3 registration study, to continue long-term idursulfase therapy and to allow placebo participants in TKT024 to receive active idursulfase treatment. The first participant enrolled on 13 Sep 2004. The study was conducted at 52 sites in 17 countries.

Participants were screened for entry based on their known medical histories and previous participation in the TKT024 study. Participants had to have completed Week 53 final evaluations in the TKT024 study. Participants were not to have received any treatment with an investigational therapy other than idursulfase within 60 days of study entry.

Participant milestones

Measure	Idursulfase (0.5 mg/kg, IV, Once-weekly) Idursulfase 0.5 milligram per kilogram (mg/kg) administered by intravenous (IV) infusion once-weekly.
Overall Study STARTED	94
Overall Study Participants Treated in Phase I of Study	94
Overall Study COMPLETED	85
Overall Study NOT COMPLETED	9

Reasons for withdrawal

Measure	Idursulfase (0.5 mg/kg, IV, Once-weekly) Idursulfase 0.5 milligram per kilogram (mg/kg) administered by intravenous (IV) infusion once-weekly.
Overall Study Death	1
Overall Study Transferred to Study TKT031NPU	7
Overall Study Returned to country of origin	1

Baseline Characteristics

Extension of Study TKT024 Evaluating Long-Term Safety and Clinical Outcomes in MPS II Patients Receiving Idursulfase

Baseline characteristics by cohort

Measure	Idursulfase (0.5 mg/kg, IV, Once-weekly) n=94 Participants Idursulfase 0.5 mg/kg administered by IV infusion once-weekly.
Age, Categorical <=18 years	70 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	24 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	14.52 years STANDARD_DEVIATION 6.634 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	94 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	15 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	79 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants
Race (NIH/OMB) Asian	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants
Race (NIH/OMB) White	78 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
Region of Enrollment Europe	40 Participants n=5 Participants
Region of Enrollment North America	34 Participants n=5 Participants
Region of Enrollment South America	20 Participants n=5 Participants
Baseline Percent Predicted Forced Vital Capacity (FVC)	56.160 percent predicted FVC STANDARD_DEVIATION 14.897 • n=5 Participants
Baseline Distance Walked in the 6-minute Walk Test (6MWT)	400.3 meters (m) STANDARD_DEVIATION 100.25 • n=5 Participants
Baseline Passive Joint Range of Motion (JROM)	67.44 percentage of JROM STANDARD_DEVIATION 9.042 • n=5 Participants
Baseline Combined Liver and Spleen Volume	1504.8 cubic centimeters (cc) STANDARD_DEVIATION 417.21 • n=5 Participants
Baseline Normalized Urine Glycosaminoglycans (GAG) Levels	361.96 microgram(mcg)GAG/mg creatinine STANDARD_DEVIATION 136.132 • n=5 Participants
Baseline Cardiac Left Ventricular Mass Index (LVMI)	97.64 gram per meter^2 (g/m^2) STANDARD_DEVIATION 36.606 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and at Week 105

Population: All participants for whom percent predicted FVC were recorded at baseline and at Week 105.

Determined by spirometry. The change is calculated as Week 105 minus baseline.

Outcome measures

Measure	Idursulfase (0.5 mg/kg, IV, Once-weekly) n=85 Participants Idursulfase 0.5 mg/kg administered by IV infusion once-weekly.
Change From Baseline in Mean Percent Predicted Forced Vital Capacity (FVC) at Week 105	-0.056 percent predicted FVC Standard Error 1.059

PRIMARY outcome

Timeframe: Baseline and at Week 105

Population: All participants for whom distance walked was recorded at baseline and at Week 105.

Determined on a walking course. The change was calculated as Week 105 minus baseline.

Outcome measures

Measure	Idursulfase (0.5 mg/kg, IV, Once-weekly) n=85 Participants Idursulfase 0.5 mg/kg administered by IV infusion once-weekly.
Change From Baseline in Mean Distance Walked in the 6-minute Walk Test (6MWT) at Week 105	23.0 meters (m) Standard Error 7.94

SECONDARY outcome

Timeframe: Baseline and at Week 105

Population: All participants for whom passive JROM were recorded at baseline and at Week 105.

Change was calculated as Week 105 minus baseline. Global JROM (% normal range of motion) is the average of 11 ratios multiplied by 100. Ratios are Left/Right means of passive range of motion in Shoulder (Flexion/Extension, Abduction, Internal/External Rotation), Elbow (Flexion/Extension), Wrist (Flexion/Extension), Index Finger (Flexion/Extension [Combined Metacarpophalangeal joint (MCP), Proximal interphalangeal joint (PIP), Distal interphalangeal joint (DIP) motion]), Hip (Flexion/Extension, Abduction, Internal/External Rotation), Knee (Flexion/Extension), and Ankle (Dorsiflexion) divided by the normal range (American Academy of Orthopedic Surgeons and American Medical Association).

Outcome measures

Measure	Idursulfase (0.5 mg/kg, IV, Once-weekly) n=84 Participants Idursulfase 0.5 mg/kg administered by IV infusion once-weekly.
Change From Baseline in Mean Passive Joint Range of Motion (JROM) at Week 105	0.63 percentage of JROM Standard Error 0.640

SECONDARY outcome

Timeframe: Baseline and at Week 105

Population: All participants for whom combined liver and spleen volume were recorded at baseline and at Week 105.

Determined by Magnetic Resonance Imaging (MRI). The change was calculated as Week 105 minus baseline.

Outcome measures

Measure	Idursulfase (0.5 mg/kg, IV, Once-weekly) n=79 Participants Idursulfase 0.5 mg/kg administered by IV infusion once-weekly.
Change From Baseline in Mean Combined Liver and Spleen Volume at Week 105	-325.5 cubic centimeters (cc) Standard Error 36.84

SECONDARY outcome

Timeframe: Baseline and at Week 105

Population: All participants for whom normalized urine GAG levels were recorded at baseline and at Week 105.

Determined by urine testing. The change was calculated as Week 105 minus baseline.

Outcome measures

Measure	Idursulfase (0.5 mg/kg, IV, Once-weekly) n=87 Participants Idursulfase 0.5 mg/kg administered by IV infusion once-weekly.
Change From Baseline in Mean Normalized Urine Glycosaminoglycans (GAG) Levels at Week 105	-238.25 mcg GAG/mg creatinine Standard Error 13.333

SECONDARY outcome

Timeframe: Baseline and at Week 105

Population: All participants for whom cardiac LVM were recorded at baseline and at Week 105.

Determined by echocardiogram. LVMI indexed to body surface area (g/m^2). The change was calculated as Week 105 minus baseline.

Outcome measures

Measure	Idursulfase (0.5 mg/kg, IV, Once-weekly) n=71 Participants Idursulfase 0.5 mg/kg administered by IV infusion once-weekly.
Change From Baseline in Mean Cardiac Left Ventricular Mass Index (LVMI) at Week 105	3.28 g/m^2 Standard Error 3.826

Adverse Events

Idursulfase (0.5 mg/kg, IV, Once-weekly)

Serious events: 38 serious events

Other events: 94 other events

Deaths: 0 deaths

Serious adverse events

Measure	Idursulfase (0.5 mg/kg, IV, Once-weekly) n=94 participants at risk Idursulfase 0.5 mg/kg administered by IV infusion once-weekly.
General disorders Catheter Related Complications	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Gastrointestinal disorders Diarrhea NOS	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Infections and infestations Endocarditis Bacterial NOS	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Respiratory, thoracic and mediastinal disorders Epistaxis	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Gastrointestinal disorders Abdominal Hernia	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Gastrointestinal disorders Abdominal Pain NOS	2.1% 2/94 • Number of events 2 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Gastrointestinal disorders Abdominal Strangulated Hernia	2.1% 2/94 • Number of events 2 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Musculoskeletal and connective tissue disorders Acquired Claw Toe	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Injury, poisoning and procedural complications Airway Complication of Anaesthesia	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Gastrointestinal disorders Appendicitis	2.1% 2/94 • Number of events 2 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Cardiac disorders Arrhythmia (Not Otherwise Specified [NOS])	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Respiratory, thoracic and mediastinal disorders Asthma Aggravated	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Cardiac disorders Atrial Fibrillation	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Infections and infestations Bacteraemia	3.2% 3/94 • Number of events 3 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Infections and infestations Bronchopneumonia NOS	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Nervous system disorders Carpal Tunnel Syndrome	7.4% 7/94 • Number of events 7 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Injury, poisoning and procedural complications Femur Fracture	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Respiratory, thoracic and mediastinal disorders Foreign Body Aspiration	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Nervous system disorders Headache	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
General disorders Hernia NOS	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Nervous system disorders Hydrocephalus	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Nervous system disorders Hypoaesthesia	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Respiratory, thoracic and mediastinal disorders Hypoxia	1.1% 1/94 • Number of events 2 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Gastrointestinal disorders Inguinal Hernia NOS	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Musculoskeletal and connective tissue disorders Joint Contracture	2.1% 2/94 • Number of events 2 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Cardiac disorders Left Ventricular Failure	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Infections and infestations Lobar Pneumonia NOS	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neurilemmoma	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Respiratory, thoracic and mediastinal disorders Obstructive Airways Disorder NOS	2.1% 2/94 • Number of events 2 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Musculoskeletal and connective tissue disorders Osteonecrosis	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Infections and infestations Otitis Media Chronic NOS	2.1% 2/94 • Number of events 2 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Infections and infestations Otitis Media NOS	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Infections and infestations Otitis Media Serous Chronic NOS	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Infections and infestations Otitis Media Serous NOS	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Musculoskeletal and connective tissue disorders Pain in Foot	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Cardiac disorders Pericardial Effusions	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Infections and infestations Pneumonia NOS	3.2% 3/94 • Number of events 3 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Vascular disorders Poor Venous Access	10.6% 10/94 • Number of events 10 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Psychiatric disorders Psychosomatic Disease	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Skin and subcutaneous tissue disorders Rash Macular	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Respiratory, thoracic and mediastinal disorders Respiratory Distress	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Injury, poisoning and procedural complications Skin Laceration	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Infections and infestations Soft Tissue Infection NOS	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Nervous system disorders Spinal Cord Compression NOS	3.2% 3/94 • Number of events 4 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Cardiac disorders Supraventricular Tachycardia	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Respiratory, thoracic and mediastinal disorders Tracheal Stenosis	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Ear and labyrinth disorders Tympanic Membrane Disorder NOS	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Gastrointestinal disorders Umbilical Hernia NOS	3.2% 3/94 • Number of events 3 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Infections and infestations Upper Respiratory Tract Infection NOS	1.1% 1/94 • Number of events 2 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Renal and urinary disorders Urinary Retention	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Gastrointestinal disorders Vomiting NOS	1.1% 1/94 • Number of events 1 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.

Other adverse events

Measure	Idursulfase (0.5 mg/kg, IV, Once-weekly) n=94 participants at risk Idursulfase 0.5 mg/kg administered by IV infusion once-weekly.
Vascular disorders Flushing	9.6% 9/94 • Number of events 32 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Vascular disorders Hypotension NOS	6.4% 6/94 • Number of events 7 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Vascular disorders Pallor	8.5% 8/94 • Number of events 8 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Immune system disorders Seasonal allergy	6.4% 6/94 • Number of events 10 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
General disorders Catheter site pain	5.3% 5/94 • Number of events 5 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
General disorders Chest pain	9.6% 9/94 • Number of events 19 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
General disorders Fall	12.8% 12/94 • Number of events 19 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
General disorders Fatigue	12.8% 12/94 • Number of events 22 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
General disorders Gait abnormal	7.4% 7/94 • Number of events 8 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
General disorders Influenza like illness	11.7% 11/94 • Number of events 33 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
General disorders Injection site extravasation	6.4% 6/94 • Number of events 8 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
General disorders Malaise	7.4% 7/94 • Number of events 12 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
General disorders Pain nos	9.6% 9/94 • Number of events 16 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
General disorders Pyrexia	60.6% 57/94 • Number of events 187 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
General disorders Rigors	11.7% 11/94 • Number of events 17 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Injury, poisoning and procedural complications Abrasion nos	18.1% 17/94 • Number of events 24 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Injury, poisoning and procedural complications Arthropod bite	9.6% 9/94 • Number of events 11 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Injury, poisoning and procedural complications Head injury	9.6% 9/94 • Number of events 9 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Injury, poisoning and procedural complications Limb injury nos	7.4% 7/94 • Number of events 9 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Injury, poisoning and procedural complications Post procedural pain	16.0% 15/94 • Number of events 25 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Injury, poisoning and procedural complications Thermal burn	5.3% 5/94 • Number of events 6 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Investigations Neutrophil count decreased	8.5% 8/94 • Number of events 8 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Investigations White blood cell count decreased	5.3% 5/94 • Number of events 6 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Cardiac disorders Atrioventricular block first degree	8.5% 8/94 • Number of events 9 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Cardiac disorders Dilatation atrial	5.3% 5/94 • Number of events 6 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Cardiac disorders Tachycardia nos	8.5% 8/94 • Number of events 24 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Cardiac disorders Ventricular hypertrophy	6.4% 6/94 • Number of events 6 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Respiratory, thoracic and mediastinal disorders Asthma nos	6.4% 6/94 • Number of events 7 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Respiratory, thoracic and mediastinal disorders Bronchitis nos	6.4% 6/94 • Number of events 7 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Respiratory, thoracic and mediastinal disorders Bronchospasm nos	8.5% 8/94 • Number of events 19 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Respiratory, thoracic and mediastinal disorders Cough	56.4% 53/94 • Number of events 155 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea nos	14.9% 14/94 • Number of events 24 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Respiratory, thoracic and mediastinal disorders Epistaxis	8.5% 8/94 • Number of events 23 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Respiratory, thoracic and mediastinal disorders Nasal congestion	40.4% 38/94 • Number of events 100 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Respiratory, thoracic and mediastinal disorders Nasopharyngitis	41.5% 39/94 • Number of events 84 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Respiratory, thoracic and mediastinal disorders Pharyngitis	48.9% 46/94 • Number of events 102 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Respiratory, thoracic and mediastinal disorders Productive cough	7.4% 7/94 • Number of events 11 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic nos	7.4% 7/94 • Number of events 9 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Respiratory, thoracic and mediastinal disorders Rhinitis nos	14.9% 14/94 • Number of events 20 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	33.0% 31/94 • Number of events 70 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Respiratory, thoracic and mediastinal disorders Rhonchi	5.3% 5/94 • Number of events 6 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Respiratory, thoracic and mediastinal disorders Sneezing	6.4% 6/94 • Number of events 7 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Respiratory, thoracic and mediastinal disorders Wheezing	16.0% 15/94 • Number of events 28 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Blood and lymphatic system disorders Anaemia nos	5.3% 5/94 • Number of events 5 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Blood and lymphatic system disorders Carpal tunnel syndrome	20.2% 19/94 • Number of events 20 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Blood and lymphatic system disorders Dizziness	19.1% 18/94 • Number of events 27 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Blood and lymphatic system disorders Headache	56.4% 53/94 • Number of events 296 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Blood and lymphatic system disorders Hypoaesthesia	8.5% 8/94 • Number of events 11 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Blood and lymphatic system disorders Insomnia	5.3% 5/94 • Number of events 6 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Blood and lymphatic system disorders Migraine nos	5.3% 5/94 • Number of events 6 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Eye disorders Conjunctivitis	5.3% 5/94 • Number of events 5 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Eye disorders Visual acuity reduced	5.3% 5/94 • Number of events 5 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Ear and labyrinth disorders Cerumen impaction	13.8% 13/94 • Number of events 17 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Ear and labyrinth disorders Ear haemorrhage	5.3% 5/94 • Number of events 5 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Ear and labyrinth disorders Ear pain	25.5% 24/94 • Number of events 34 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Ear and labyrinth disorders Otorrhoea	28.7% 27/94 • Number of events 88 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Gastrointestinal disorders Abdominal pain nos	36.2% 34/94 • Number of events 73 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Gastrointestinal disorders Constipation	11.7% 11/94 • Number of events 15 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Gastrointestinal disorders Diarrhoea nos	34.0% 32/94 • Number of events 78 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Gastrointestinal disorders Dyspepsia	7.4% 7/94 • Number of events 19 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Gastrointestinal disorders Flatulence	5.3% 5/94 • Number of events 5 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Gastrointestinal disorders Gastroenteritis nos	10.6% 10/94 • Number of events 12 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Gastrointestinal disorders Loose stools	5.3% 5/94 • Number of events 5 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Gastrointestinal disorders Nausea	25.5% 24/94 • Number of events 44 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Gastrointestinal disorders Toothache	7.4% 7/94 • Number of events 9 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Gastrointestinal disorders Umbilical hernia nos	5.3% 5/94 • Number of events 5 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Gastrointestinal disorders Vomiting nos	41.5% 39/94 • Number of events 102 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Hepatobiliary disorders Hepatomegaly	5.3% 5/94 • Number of events 5 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Skin and subcutaneous tissue disorders Acne nos	14.9% 14/94 • Number of events 17 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Skin and subcutaneous tissue disorders Contusion	9.6% 9/94 • Number of events 10 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Skin and subcutaneous tissue disorders Eczema	7.4% 7/94 • Number of events 9 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Skin and subcutaneous tissue disorders Erythema	11.7% 11/94 • Number of events 35 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Skin and subcutaneous tissue disorders Pruritus	11.7% 11/94 • Number of events 27 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Skin and subcutaneous tissue disorders Rash macular	6.4% 6/94 • Number of events 11 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Skin and subcutaneous tissue disorders Rash nos	21.3% 20/94 • Number of events 60 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Skin and subcutaneous tissue disorders Rash papular	6.4% 6/94 • Number of events 8 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Skin and subcutaneous tissue disorders Rash pruritic	10.6% 10/94 • Number of events 16 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Skin and subcutaneous tissue disorders Skin lesion nos	9.6% 9/94 • Number of events 13 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Skin and subcutaneous tissue disorders Urticaria nos	14.9% 14/94 • Number of events 54 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Musculoskeletal and connective tissue disorders Arthralgia	41.5% 39/94 • Number of events 81 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Musculoskeletal and connective tissue disorders Back pain	24.5% 23/94 • Number of events 39 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	5.3% 5/94 • Number of events 7 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Musculoskeletal and connective tissue disorders Myalgia	11.7% 11/94 • Number of events 13 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Musculoskeletal and connective tissue disorders Neck pain	18.1% 17/94 • Number of events 24 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Musculoskeletal and connective tissue disorders Pain in foot	5.3% 5/94 • Number of events 7 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Musculoskeletal and connective tissue disorders Pain in limb	30.9% 29/94 • Number of events 59 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Infections and infestations Ear infection nos	38.3% 36/94 • Number of events 91 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Infections and infestations Furuncle	5.3% 5/94 • Number of events 5 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Infections and infestations Influenza	7.4% 7/94 • Number of events 11 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Infections and infestations Localised infection	5.3% 5/94 • Number of events 5 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Infections and infestations Lower respiratory tract infection nos	7.4% 7/94 • Number of events 11 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Infections and infestations Otitis media nos	23.4% 22/94 • Number of events 37 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Infections and infestations Otitis media serous nos	7.4% 7/94 • Number of events 9 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Infections and infestations Pneumonia nos	7.4% 7/94 • Number of events 9 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Infections and infestations Respiratory tract infection nos	6.4% 6/94 • Number of events 12 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Infections and infestations Sinusitis nos	9.6% 9/94 • Number of events 16 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Infections and infestations Skin fungal infection nos	8.5% 8/94 • Number of events 9 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Infections and infestations Tinea pedis	6.4% 6/94 • Number of events 21 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Infections and infestations Tonsillitis	6.4% 6/94 • Number of events 6 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Infections and infestations Tooth caries nos	7.4% 7/94 • Number of events 8 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Infections and infestations Upper respiratory tract infection nos	50.0% 47/94 • Number of events 106 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Infections and infestations Upper respiratory tract infection viral nos	9.6% 9/94 • Number of events 13 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.
Infections and infestations Viral infection nos	10.6% 10/94 • Number of events 12 • Adverse events were assessed throughout the duration of the TKT024EXT study. Adverse events were monitored from the time the first participant signed the informed consent until approximately 30 days after the last study visit. The "Serious Adverse Events" table lists all serious adverse events that occurred during the study regardless of a relationship to the study drug. The "Other Adverse Events" table lists those non-serious adverse events that were were determined to be possibly related to the study drug.

Additional Information

Study Director

Shire

Phone: +1 866 842 5335

Email: ClinicalTransparency@shire.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER