Trial Outcomes & Findings for Methotrexate and Mycophenolate Mofetil for UVEITIS (NCT NCT01829295)

NCT ID: NCT01829295

Last Updated: 2024-04-02

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

216 participants

Primary outcome timeframe

6 Months

Results posted on

2024-04-02

Participant Flow

Participant milestones

Participant milestones
Measure	Methotrexate Only oral methotrexate Methotrexate: For the first two weeks, an introductory dose of 15 mg/week (7.5mg twice a day (BID) once a week) orally. After two weeks, the dose will be increased to 25 mg/week (12.5mg BID once a week) Prednisone: All patients enrolled in the study will be initially taking concomitant oral corticosteroids at 1 mg/kg or 60 mg daily, whichever is less. Initial corticosteroid dose will be continued for 2 to 4 weeks at which point prednisone will be gradually tapered. Prednisone will be tapered to and held at 7.5 mg/day for the first 6 months of the study. These patients never switched over to receive mycophenolate mofetil as they were a treatment success at Month 6.	Mycophenolate Mofetil Only oral mycophenolate mofetil Mycophenolate mofetil: For the first two weeks, an introductory dose of 500 mg BID orally. After two weeks, the dose will be increased to 1.5 g BID. Prednisone: All patients enrolled in the study will be initially taking concomitant oral corticosteroids at 1 mg/kg or 60 mg daily, whichever is less. Initial corticosteroid dose will be continued for 2 to 4 weeks at which point prednisone will be gradually tapered. Prednisone will be tapered to and held at 7.5 mg/day for the first 6 months of the study. These patients never switched over to receive mycophenolate mofetil as they were a treatment success at Month 6.	Methotrexate, Then Mycophenolate Mofetil first received oral methotrexate Methotrexate: For the first two weeks, an introductory dose of 15 mg/week (7.5mg BID once a week) orally. After two weeks, the dose will be increased to 25 mg/week (12.5mg BID once a week) Prednisone: All patients enrolled in the study will be initially taking concomitant oral corticosteroids at 1 mg/kg or 60 mg daily, whichever is less. Initial corticosteroid dose will be continued for 2 to 4 weeks at which point prednisone will be gradually tapered. Prednisone will be tapered to and held at 7.5 mg/day for the first 6 months of the study. then switched over to receive oral mycophenolate mofetil after failing with oral methotrexate Mycophenolate mofetil: For the first two weeks, an introductory dose of 500 mg BID orally. After two weeks, the dose will be increased to 1.5 g BID. Followed the same prednisone schedule as described in the Methotrexate only and Mycophenolate Mofetil only groups.	Mycophenolate Mofetil, Then Methotrexate first received oral mycophenolate mofetil Mycophenolate mofetil: For the first two weeks, an introductory dose of 500 mg BID orally. After two weeks, the dose will be increased to 1.5 g BID. Prednisone: All patients enrolled in the study will be initially taking concomitant oral corticosteroids at 1 mg/kg or 60 mg daily, whichever is less. Initial corticosteroid dose will be continued for 2 to 4 weeks at which point prednisone will be gradually tapered. Prednisone will be tapered to and held at 7.5 mg/day for the first 6 months of the study. then switched over to receive oral mycophenolate mofetil after failing with oral mycophenolate mofetil Methotrexate: For the first two weeks, an introductory dose of 15 mg/week (7.5mg BID once a week) orally. After two weeks, the dose will be increased to 25 mg/week (12.5mg BID once a week) Followed the same prednisone schedule as described in the Methotrexate only and Mycophenolate Mofetil only groups.
0-6 Months STARTED	107	109	0	0
0-6 Months COMPLETED	96	98	0	0
0-6 Months NOT COMPLETED	11	11	0	0
6-12 Months STARTED	64	56	32	42
6-12 Months COMPLETED	60	54	20	29
6-12 Months NOT COMPLETED	4	2	12	13

Reasons for withdrawal

Reasons for withdrawal
Measure	Methotrexate Only oral methotrexate Methotrexate: For the first two weeks, an introductory dose of 15 mg/week (7.5mg twice a day (BID) once a week) orally. After two weeks, the dose will be increased to 25 mg/week (12.5mg BID once a week) Prednisone: All patients enrolled in the study will be initially taking concomitant oral corticosteroids at 1 mg/kg or 60 mg daily, whichever is less. Initial corticosteroid dose will be continued for 2 to 4 weeks at which point prednisone will be gradually tapered. Prednisone will be tapered to and held at 7.5 mg/day for the first 6 months of the study. These patients never switched over to receive mycophenolate mofetil as they were a treatment success at Month 6.	Mycophenolate Mofetil Only oral mycophenolate mofetil Mycophenolate mofetil: For the first two weeks, an introductory dose of 500 mg BID orally. After two weeks, the dose will be increased to 1.5 g BID. Prednisone: All patients enrolled in the study will be initially taking concomitant oral corticosteroids at 1 mg/kg or 60 mg daily, whichever is less. Initial corticosteroid dose will be continued for 2 to 4 weeks at which point prednisone will be gradually tapered. Prednisone will be tapered to and held at 7.5 mg/day for the first 6 months of the study. These patients never switched over to receive mycophenolate mofetil as they were a treatment success at Month 6.	Methotrexate, Then Mycophenolate Mofetil first received oral methotrexate Methotrexate: For the first two weeks, an introductory dose of 15 mg/week (7.5mg BID once a week) orally. After two weeks, the dose will be increased to 25 mg/week (12.5mg BID once a week) Prednisone: All patients enrolled in the study will be initially taking concomitant oral corticosteroids at 1 mg/kg or 60 mg daily, whichever is less. Initial corticosteroid dose will be continued for 2 to 4 weeks at which point prednisone will be gradually tapered. Prednisone will be tapered to and held at 7.5 mg/day for the first 6 months of the study. then switched over to receive oral mycophenolate mofetil after failing with oral methotrexate Mycophenolate mofetil: For the first two weeks, an introductory dose of 500 mg BID orally. After two weeks, the dose will be increased to 1.5 g BID. Followed the same prednisone schedule as described in the Methotrexate only and Mycophenolate Mofetil only groups.	Mycophenolate Mofetil, Then Methotrexate first received oral mycophenolate mofetil Mycophenolate mofetil: For the first two weeks, an introductory dose of 500 mg BID orally. After two weeks, the dose will be increased to 1.5 g BID. Prednisone: All patients enrolled in the study will be initially taking concomitant oral corticosteroids at 1 mg/kg or 60 mg daily, whichever is less. Initial corticosteroid dose will be continued for 2 to 4 weeks at which point prednisone will be gradually tapered. Prednisone will be tapered to and held at 7.5 mg/day for the first 6 months of the study. then switched over to receive oral mycophenolate mofetil after failing with oral mycophenolate mofetil Methotrexate: For the first two weeks, an introductory dose of 15 mg/week (7.5mg BID once a week) orally. After two weeks, the dose will be increased to 25 mg/week (12.5mg BID once a week) Followed the same prednisone schedule as described in the Methotrexate only and Mycophenolate Mofetil only groups.
6-12 Months Did not want to switch antimetabolites	0	0	9	11
6-12 Months Adverse Event	0	0	3	2
6-12 Months Lost to Follow-up	2	0	0	0
6-12 Months Withdrawal by Subject	2	2	0	0

Baseline Characteristics

Methotrexate and Mycophenolate Mofetil for UVEITIS

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Methotrexate n=107 Participants oral methotrexate Methotrexate: For the first two weeks, an introductory dose of 15 mg/week (7.5mg BID once a week) orally. After two weeks, the dose will be increased to 25 mg/week (12.5mg BID once a week) Prednisone: All patients enrolled in the study will be initially taking concomitant oral corticosteroids at 1 mg/kg or 60 mg daily, whichever is less. Initial corticosteroid dose will be continued for 2 to 4 weeks at which point prednisone will be gradually tapered. Prednisone will be tapered to and held at 7.5 mg/day for the first 6 months of the study.	Mycophenolate Mofetil n=109 Participants oral mycophenolate mofetil Mycophenolate mofetil: For the first two weeks, an introductory dose of 500 mg BID orally. After two weeks, the dose will be increased to 1.5 g BID. Prednisone: All patients enrolled in the study will be initially taking concomitant oral corticosteroids at 1 mg/kg or 60 mg daily, whichever is less. Initial corticosteroid dose will be continued for 2 to 4 weeks at which point prednisone will be gradually tapered. Prednisone will be tapered to and held at 7.5 mg/day for the first 6 months of the study.	Total n=216 Participants Total of all reporting groups
Age, Continuous	36 years n=5 Participants	41 years n=7 Participants	38 years n=5 Participants
Sex: Female, Male Female	75 Participants n=5 Participants	60 Participants n=7 Participants	135 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=5 Participants	49 Participants n=7 Participants	81 Participants n=5 Participants
Race/Ethnicity, Customized White	25 participants n=5 Participants	22 participants n=7 Participants	47 participants n=5 Participants
Race/Ethnicity, Customized Black	3 participants n=5 Participants	6 participants n=7 Participants	9 participants n=5 Participants
Race/Ethnicity, Customized Asian	5 participants n=5 Participants	6 participants n=7 Participants	11 participants n=5 Participants
Race/Ethnicity, Customized Indian Subcontinent	70 participants n=5 Participants	69 participants n=7 Participants	139 participants n=5 Participants
Race/Ethnicity, Customized Native American	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Race/Ethnicity, Customized Pacific Islander	1 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants
Race/Ethnicity, Customized Middle Eastern	5 participants n=5 Participants	5 participants n=7 Participants	10 participants n=5 Participants
Region of Enrollment Saudi Arabia	4 participants n=5 Participants	5 participants n=7 Participants	9 participants n=5 Participants
Region of Enrollment United States	22 participants n=5 Participants	25 participants n=7 Participants	47 participants n=5 Participants
Region of Enrollment Mexico	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment Australia	11 participants n=5 Participants	10 participants n=7 Participants	21 participants n=5 Participants
Region of Enrollment India	69 participants n=5 Participants	67 participants n=7 Participants	136 participants n=5 Participants
Anatomic Location of Uveitis Intermediate	8 Participants n=5 Participants	9 Participants n=7 Participants	17 Participants n=5 Participants
Anatomic Location of Uveitis Anterior + Intermediate	15 Participants n=5 Participants	14 Participants n=7 Participants	29 Participants n=5 Participants
Anatomic Location of Uveitis Posterior	24 Participants n=5 Participants	25 Participants n=7 Participants	49 Participants n=5 Participants
Anatomic Location of Uveitis Panuveitis	60 Participants n=5 Participants	61 Participants n=7 Participants	121 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 Months

Population: All randomized patient with a 6-month visit, or who were declared early treatment failures, are included.

Outcome measures

Outcome measures
Measure	Methotrexate n=96 Participants oral methotrexate Methotrexate: For the first two weeks, an introductory dose of 15 mg/week (7.5mg BID once a week) orally. After two weeks, the dose will be increased to 25 mg/week (12.5mg BID once a week) Prednisone: All patients enrolled in the study will be initially taking concomitant oral corticosteroids at 1 mg/kg or 60 mg daily, whichever is less. Initial corticosteroid dose will be continued for 2 to 4 weeks at which point prednisone will be gradually tapered. Prednisone will be tapered to and held at 7.5 mg/day for the first 6 months of the study.	Mycophenolate Mofetil n=98 Participants oral mycophenolate mofetil Mycophenolate mofetil: For the first two weeks, an introductory dose of 500 mg BID orally. After two weeks, the dose will be increased to 1.5 g BID. Prednisone: All patients enrolled in the study will be initially taking concomitant oral corticosteroids at 1 mg/kg or 60 mg daily, whichever is less. Initial corticosteroid dose will be continued for 2 to 4 weeks at which point prednisone will be gradually tapered. Prednisone will be tapered to and held at 7.5 mg/day for the first 6 months of the study.
Number of Participants Achieving Treatment Success at 6 Months (Phase I, 0-6 Months)	64 Participants	56 Participants

SECONDARY outcome

Timeframe: 12 Months

Population: Patients who were a treatment success at 6 months and continued in follow-up.

Controlled ocular inflammation (≤ 0.5+ anterior chamber cells, ≤ 0.5+ vitreous haze, no active retinal/choroidal lesions in both eyes) with 7.5 mg/day of oral prednisone and ≤ 2 drops/day of topical 1% prednisolone acetate in patients who were a treatment success at the primary outcome of 6 months.

Outcome measures

Outcome measures
Measure	Methotrexate n=60 Participants oral methotrexate Methotrexate: For the first two weeks, an introductory dose of 15 mg/week (7.5mg BID once a week) orally. After two weeks, the dose will be increased to 25 mg/week (12.5mg BID once a week) Prednisone: All patients enrolled in the study will be initially taking concomitant oral corticosteroids at 1 mg/kg or 60 mg daily, whichever is less. Initial corticosteroid dose will be continued for 2 to 4 weeks at which point prednisone will be gradually tapered. Prednisone will be tapered to and held at 7.5 mg/day for the first 6 months of the study.	Mycophenolate Mofetil n=54 Participants oral mycophenolate mofetil Mycophenolate mofetil: For the first two weeks, an introductory dose of 500 mg BID orally. After two weeks, the dose will be increased to 1.5 g BID. Prednisone: All patients enrolled in the study will be initially taking concomitant oral corticosteroids at 1 mg/kg or 60 mg daily, whichever is less. Initial corticosteroid dose will be continued for 2 to 4 weeks at which point prednisone will be gradually tapered. Prednisone will be tapered to and held at 7.5 mg/day for the first 6 months of the study.
Number of Participants Achieving Treatment Success at 12 Months on Same Medication (Phase I, 6-12 Months)	48 Participants	40 Participants

SECONDARY outcome

Timeframe: 6 Months

Population: Patients who switched to the other medication following treatment failure at 6 months (or earlier). Patients were analyzed by the medication that they received in this second phase (Phase II, 0-6 Months).

Controlled ocular inflammation (≤ 0.5+ anterior chamber cells, ≤ 0.5+ vitreous haze, no active retinal/choroidal lesions in both eyes) with 7.5 mg/day of oral prednisone and ≤ 2 drops/day of topical 1% prednisolone acetate for patients who crossed over to other medication following treatment failure at 6 months (or earlier).

Outcome measures

Outcome measures
Measure	Methotrexate n=29 Participants oral methotrexate Methotrexate: For the first two weeks, an introductory dose of 15 mg/week (7.5mg BID once a week) orally. After two weeks, the dose will be increased to 25 mg/week (12.5mg BID once a week) Prednisone: All patients enrolled in the study will be initially taking concomitant oral corticosteroids at 1 mg/kg or 60 mg daily, whichever is less. Initial corticosteroid dose will be continued for 2 to 4 weeks at which point prednisone will be gradually tapered. Prednisone will be tapered to and held at 7.5 mg/day for the first 6 months of the study.	Mycophenolate Mofetil n=20 Participants oral mycophenolate mofetil Mycophenolate mofetil: For the first two weeks, an introductory dose of 500 mg BID orally. After two weeks, the dose will be increased to 1.5 g BID. Prednisone: All patients enrolled in the study will be initially taking concomitant oral corticosteroids at 1 mg/kg or 60 mg daily, whichever is less. Initial corticosteroid dose will be continued for 2 to 4 weeks at which point prednisone will be gradually tapered. Prednisone will be tapered to and held at 7.5 mg/day for the first 6 months of the study.
Number of Participants Achieving Treatment Success After Switching to Other Medication (Phase II, 0-6 Months)	20 Participants	7 Participants

Adverse Events

Methotrexate

Serious events: 7 serious events

Other events: 99 other events

Deaths: 1 deaths

Mycophenolate Mofetil

Serious events: 7 serious events

Other events: 100 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Methotrexate n=107 participants at risk oral methotrexate Patients randomized to receive oral methotrexate in Phase I, 0-6 Months. Methotrexate: For the first two weeks, an introductory dose of 15 mg/week (7.5mg BID once a week) orally. After two weeks, the dose will be increased to 25 mg/week (12.5mg BID once a week) Prednisone: All patients enrolled in the study will be initially taking concomitant oral corticosteroids at 1 mg/kg or 60 mg daily, whichever is less. Initial corticosteroid dose will be continued for 2 to 4 weeks at which point prednisone will be gradually tapered. Prednisone will be tapered to and held at 7.5 mg/day for the first 6 months of the study.	Mycophenolate Mofetil n=109 participants at risk oral mycophenolate mofetil Patients randomized to receive oral mycophenolate mofetil in Phase I, 0-6 Months. Mycophenolate mofetil: For the first two weeks, an introductory dose of 500 mg BID orally. After two weeks, the dose will be increased to 1.5 g BID. Prednisone: All patients enrolled in the study will be initially taking concomitant oral corticosteroids at 1 mg/kg or 60 mg daily, whichever is less. Initial corticosteroid dose will be continued for 2 to 4 weeks at which point prednisone will be gradually tapered. Prednisone will be tapered to and held at 7.5 mg/day for the first 6 months of the study.
Eye disorders Glaucoma	0.00% 0/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	0.92% 1/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
Eye disorders Retinal detachment	0.93% 1/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	0.00% 0/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
Blood and lymphatic system disorders SGOT and SGPT	2.8% 3/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	1.8% 2/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
Renal and urinary disorders Diarrhea	0.00% 0/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	0.92% 1/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
Musculoskeletal and connective tissue disorders Disability or permanent damage	0.93% 1/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	0.00% 0/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
General disorders Hospitalization	1.9% 2/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	1.8% 2/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
Infections and infestations Serious systemic infection	0.00% 0/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	0.92% 1/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
Gastrointestinal disorders Vomiting	0.93% 1/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	0.00% 0/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
General disorders Other serious/systemic event	2.8% 3/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	0.92% 1/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
General disorders Death	0.93% 1/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	0.00% 0/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.

Other adverse events

Additional Information

Dr. Nisha Acharya

F.I. Proctor Foundation, UCSF

Phone: 4154768131

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Methotrexate n=107 participants at risk oral methotrexate Patients randomized to receive oral methotrexate in Phase I, 0-6 Months. Methotrexate: For the first two weeks, an introductory dose of 15 mg/week (7.5mg BID once a week) orally. After two weeks, the dose will be increased to 25 mg/week (12.5mg BID once a week) Prednisone: All patients enrolled in the study will be initially taking concomitant oral corticosteroids at 1 mg/kg or 60 mg daily, whichever is less. Initial corticosteroid dose will be continued for 2 to 4 weeks at which point prednisone will be gradually tapered. Prednisone will be tapered to and held at 7.5 mg/day for the first 6 months of the study.	Mycophenolate Mofetil n=109 participants at risk oral mycophenolate mofetil Patients randomized to receive oral mycophenolate mofetil in Phase I, 0-6 Months. Mycophenolate mofetil: For the first two weeks, an introductory dose of 500 mg BID orally. After two weeks, the dose will be increased to 1.5 g BID. Prednisone: All patients enrolled in the study will be initially taking concomitant oral corticosteroids at 1 mg/kg or 60 mg daily, whichever is less. Initial corticosteroid dose will be continued for 2 to 4 weeks at which point prednisone will be gradually tapered. Prednisone will be tapered to and held at 7.5 mg/day for the first 6 months of the study.
Eye disorders Cataract	4.7% 5/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	1.8% 2/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
Eye disorders Suspected/confirmed glaucoma diagnosis	1.9% 2/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	1.8% 2/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
Eye disorders Hypotony	0.00% 0/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	0.92% 1/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
Eye disorders Ocular hypertension	9.3% 10/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	11.9% 13/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
Eye disorders Peripheral and/or central vitreous hemorrhage	2.8% 3/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	2.8% 3/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
Eye disorders Other ocular event	25.2% 27/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	23.9% 26/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
General disorders Creatinine	0.93% 1/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	0.00% 0/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
General disorders Hemoglobin	1.9% 2/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	2.8% 3/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
General disorders Leukocytes	2.8% 3/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	0.92% 1/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
General disorders SGOT or SGPT	13.1% 14/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	7.3% 8/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
General disorders Allergic reaction	13.1% 14/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	10.1% 11/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
Cardiac disorders Mild congestive heart failure or arrhythmia	3.7% 4/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	1.8% 2/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
Renal and urinary disorders Diarrhea	23.4% 25/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	22.0% 24/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
General disorders Dyspnea	19.6% 21/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	20.2% 22/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
General disorders Fatigue	57.9% 62/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	54.1% 59/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
General disorders Fever	10.3% 11/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	16.5% 18/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
General disorders Hair loss	5.6% 6/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	1.8% 2/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
General disorders Headache	51.4% 55/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	41.3% 45/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
Infections and infestations Non-serious systemic infection	23.4% 25/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	24.8% 27/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
Psychiatric disorders Mood changes	30.8% 33/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	23.9% 26/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
Musculoskeletal and connective tissue disorders Muscle weakness	29.9% 32/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	23.9% 26/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
General disorders Nausea	39.3% 42/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	27.5% 30/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
Nervous system disorders Numbness/tingling	23.4% 25/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	16.5% 18/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
General disorders Vomiting	24.3% 26/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	22.0% 24/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
General disorders Other systemic (no treatment required)	60.7% 65/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	57.8% 63/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
Eye disorders Decrease in vision/defective vision	8.4% 9/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	17.4% 19/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.
Eye disorders Eye pain	8.4% 9/107 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.	3.7% 4/109 • Adverse event data were collected through the primary endpoint (the first 6 months) for each enrolled patient; Phase I, 0-6 Months.