Trial Outcomes & Findings for Long-Term Study of Nitisinone to Treat Alkaptonuria (NCT NCT00107783)
NCT ID: NCT00107783
Last Updated: 2021-08-26
Results Overview
Change from baseline in the total (external + internal) hip range of motion (ROM) in the worse hip at 36 months. The patient lies on exam table in the supine position. The patient flexes his/her hip and knee to 90 degrees. The examiner measures the patient's hip external rotation and hip internal rotation range of motion with a goniometer.
COMPLETED
PHASE2
40 participants
Measured at baseline and at 36 months
2021-08-26
Participant Flow
Patients were enrolled at the NIH Clinical Center between April 2005 and March 2006.
Participant milestones
| Measure |
Control
No treatment
|
Nitisinone-treated
Subjects received nitisinone 2 mg orally, once daily.
|
|---|---|---|
|
Overall Study
STARTED
|
20
|
20
|
|
Overall Study
COMPLETED
|
17
|
16
|
|
Overall Study
NOT COMPLETED
|
3
|
4
|
Reasons for withdrawal
| Measure |
Control
No treatment
|
Nitisinone-treated
Subjects received nitisinone 2 mg orally, once daily.
|
|---|---|---|
|
Overall Study
Adverse Event
|
0
|
2
|
|
Overall Study
Death
|
0
|
1
|
|
Overall Study
Withdrawal by Subject
|
2
|
0
|
|
Overall Study
Second hip replacement
|
1
|
1
|
Baseline Characteristics
Long-Term Study of Nitisinone to Treat Alkaptonuria
Baseline characteristics by cohort
| Measure |
Control
n=20 Participants
No treatment
|
Nitisinone-treated
n=20 Participants
Subjects received nitisinone 2 mg orally, once daily.
|
Total
n=40 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
20 Participants
n=99 Participants
|
19 Participants
n=107 Participants
|
39 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
1 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Age, Continuous
|
51.3 years
STANDARD_DEVIATION 6.5 • n=99 Participants
|
52.2 years
STANDARD_DEVIATION 7.9 • n=107 Participants
|
51.7 years
STANDARD_DEVIATION 7.1 • n=206 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
13 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
15 Participants
n=99 Participants
|
12 Participants
n=107 Participants
|
27 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
20 participants
n=99 Participants
|
20 participants
n=107 Participants
|
40 participants
n=206 Participants
|
|
Total Range of Motion (ROM) Worse Hip
|
46.4 degrees
STANDARD_DEVIATION 16.1 • n=99 Participants
|
39.0 degrees
STANDARD_DEVIATION 12.7 • n=107 Participants
|
42.7 degrees
STANDARD_DEVIATION 14.8 • n=206 Participants
|
|
Schober's test
|
11.42 cm
STANDARD_DEVIATION 1.04 • n=99 Participants
|
10.86 cm
STANDARD_DEVIATION 0.73 • n=107 Participants
|
11.14 cm
STANDARD_DEVIATION 0.93 • n=206 Participants
|
|
Functional Reach Assessment
|
10.22 cm
STANDARD_DEVIATION 2.92 • n=99 Participants
|
8.98 cm
STANDARD_DEVIATION 3.10 • n=107 Participants
|
9.60 cm
STANDARD_DEVIATION 3.04 • n=206 Participants
|
|
Timed get up and go
|
7.56 seconds
STANDARD_DEVIATION 1.40 • n=99 Participants
|
9.70 seconds
STANDARD_DEVIATION 4.10 • n=107 Participants
|
8.63 seconds
STANDARD_DEVIATION 3.21 • n=206 Participants
|
|
6 minute walk test
|
1578 ft
STANDARD_DEVIATION 205 • n=99 Participants
|
1336 ft
STANDARD_DEVIATION 369 • n=107 Participants
|
1457 ft
STANDARD_DEVIATION 319 • n=206 Participants
|
PRIMARY outcome
Timeframe: Measured at baseline and at 36 monthsPopulation: Intention to treat.
Change from baseline in the total (external + internal) hip range of motion (ROM) in the worse hip at 36 months. The patient lies on exam table in the supine position. The patient flexes his/her hip and knee to 90 degrees. The examiner measures the patient's hip external rotation and hip internal rotation range of motion with a goniometer.
Outcome measures
| Measure |
Control
n=20 Participants
No treatment
|
Nitisinone-treated
n=20 Participants
Subjects received nitisinone 2 mg orally, once daily.
|
|---|---|---|
|
Change in Total ROM Worse Hip
|
-9.1 degrees
Standard Deviation 24.7
|
1.6 degrees
Standard Deviation 21.8
|
SECONDARY outcome
Timeframe: Measured at baseline and at 36 monthsPopulation: In the control group, two patients who dropped out for personal reasons were not included in this analysis, and in the treated group one patient who died was not included in this analysis.
Change from baseline of Schober's test at 36 months. Schober's test measures a patient's ability to flex his/her lower back. The examiner makes a mark at L5 (fifth lumbar vertebra) and places one finger 5 cm below and another finger 10 cm above this mark. The patient is asked to touch his/her toes. The examiner measures the increase in distance between the two fingers.
Outcome measures
| Measure |
Control
n=18 Participants
No treatment
|
Nitisinone-treated
n=19 Participants
Subjects received nitisinone 2 mg orally, once daily.
|
|---|---|---|
|
Change in Schober's Test
|
-0.06 cm
Standard Deviation 1.33
|
0.12 cm
Standard Deviation 1.05
|
SECONDARY outcome
Timeframe: Measured at baseline and at 36 monthsPopulation: In the control group, two patients who dropped out for personal reasons were not included in this analysis, and in the treated group one patient who died was not included in this analysis.
Change from baseline of functional reach assessment at 36 months. Functional reach assessment measures the difference between the length of a person's outstretched arm and their maximal reach forward, while maintaining balance.
Outcome measures
| Measure |
Control
n=18 Participants
No treatment
|
Nitisinone-treated
n=19 Participants
Subjects received nitisinone 2 mg orally, once daily.
|
|---|---|---|
|
Change in Functional Reach Assessment
|
-1.21 cm
Standard Deviation 3.81
|
-1.86 cm
Standard Deviation 3.59
|
SECONDARY outcome
Timeframe: Measured at baseline and at 36 monthsPopulation: In the control group, two patients who dropped out for personal reasons were not included in this analysis, and in the treated group one patient who died was not included in this analysis.
Change from baseline of timed get up and go at 36 months. In timed get up and go, the patient is asked to stand up from a standard chair and walk a distance of 3 meters, turn around and walk back to the chair and sit down. The examiner measures the time it takes for the patient to perform this series of tasks.
Outcome measures
| Measure |
Control
n=18 Participants
No treatment
|
Nitisinone-treated
n=19 Participants
Subjects received nitisinone 2 mg orally, once daily.
|
|---|---|---|
|
Change in Timed Get up and go
|
-0.54 seconds
Standard Deviation 1.84
|
-1.33 seconds
Standard Deviation 5.04
|
SECONDARY outcome
Timeframe: Measured at baseline and at 36 monthsPopulation: In the control group, two patients who dropped out for personal reasons were not included in this analysis, and in the treated group one patient who died was not included in this analysis.
Change from baseline of the 6MWT at 36 months. The 6MWT measures the distance that a patient can quickly walk on a flat hard surface in a period of six minutes.
Outcome measures
| Measure |
Control
n=18 Participants
No treatment
|
Nitisinone-treated
n=19 Participants
Subjects received nitisinone 2 mg orally, once daily.
|
|---|---|---|
|
Change in 6 Minute Walk Test (6MWT)
|
22 ft
Standard Deviation 356
|
169 ft
Standard Deviation 591
|
Adverse Events
Control
Nitisinone-treated
Serious adverse events
| Measure |
Control
n=20 participants at risk
No treatment
|
Nitisinone-treated
n=20 participants at risk
Subjects received nitisinone 2 mg orally, once daily.
|
|---|---|---|
|
Cardiac disorders
atrial fibrillation
|
0.00%
0/20 • 36 months
|
5.0%
1/20 • Number of events 1 • 36 months
|
|
Eye disorders
keratitis
|
0.00%
0/20 • 36 months
|
5.0%
1/20 • Number of events 3 • 36 months
|
|
Hepatobiliary disorders
bile duct stone
|
0.00%
0/20 • 36 months
|
5.0%
1/20 • Number of events 1 • 36 months
|
|
Injury, poisoning and procedural complications
accidental overdose
|
0.00%
0/20 • 36 months
|
5.0%
1/20 • Number of events 1 • 36 months
|
|
Hepatobiliary disorders
liver enzyme elevation
|
0.00%
0/20 • 36 months
|
5.0%
1/20 • Number of events 1 • 36 months
|
|
Injury, poisoning and procedural complications
muscle injury
|
0.00%
0/20 • 36 months
|
5.0%
1/20 • Number of events 1 • 36 months
|
|
Blood and lymphatic system disorders
anemia
|
0.00%
0/20 • 36 months
|
5.0%
1/20 • Number of events 1 • 36 months
|
|
Immune system disorders
sarcoidosis
|
0.00%
0/20 • 36 months
|
5.0%
1/20 • Number of events 1 • 36 months
|
Other adverse events
| Measure |
Control
n=20 participants at risk
No treatment
|
Nitisinone-treated
n=20 participants at risk
Subjects received nitisinone 2 mg orally, once daily.
|
|---|---|---|
|
Hepatobiliary disorders
elevated liver enzymes
|
30.0%
6/20 • Number of events 8 • 36 months
|
30.0%
6/20 • Number of events 8 • 36 months
|
|
Psychiatric disorders
depression
|
10.0%
2/20 • Number of events 2 • 36 months
|
0.00%
0/20 • 36 months
|
|
Infections and infestations
upper respiratory infection
|
25.0%
5/20 • Number of events 6 • 36 months
|
10.0%
2/20 • Number of events 2 • 36 months
|
|
Skin and subcutaneous tissue disorders
skin rash
|
15.0%
3/20 • Number of events 3 • 36 months
|
0.00%
0/20 • 36 months
|
|
Ear and labyrinth disorders
sensorineural hearing loss
|
—
0/0 • 36 months
|
15.0%
3/20 • Number of events 3 • 36 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place