Trial Outcomes & Findings for Efficacy and Safety of Nefecon in Patients With Primary IgA (Immunoglobulin A) Nephropathy (NCT NCT03643965)

Last Updated: 2024-12-03

Results Overview

Part A primary endpoint: The ratio of Urine Protein to Creatinine Ratio (UPCR) (based on 24-hour urine collections) at 9 months following the first dose of study drug compared to baseline. Ratio being: UPCR at 9 months in g/gram divided with UPCR at Baseline in g/gram

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

365 participants

Primary outcome timeframe

9 months

Results posted on

2024-12-03

Participant Flow

Participant milestones

Participant milestones
Measure	Nefecon Nefecon 16 mg once daily by mouth for 9 months. Nefecon: Nefecon 16 mg for daily administration by mouth for 9 months.	Placebo Oral Capsule Placebo oral capsule once daily by mouth for 9 months. Placebo oral capsule: Placebo capsules for daily administration by mouth for 9 months.
Part A STARTED	182	182
Part A COMPLETED	175	174
Part A NOT COMPLETED	7	8
Part B STARTED	175	174
Part B COMPLETED	161	165
Part B NOT COMPLETED	14	9

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Efficacy and Safety of Nefecon in Patients With Primary IgA (Immunoglobulin A) Nephropathy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nefecon n=182 Participants Nefecon 16 mg once daily by mouth for 9 months. Nefecon: Nefecon 16 mg for daily administration by mouth for 9 months.	Placebo Oral Capsule n=182 Participants Placebo oral capsule once daily by mouth for 9 months. Placebo oral capsule: Placebo capsules for daily administration by mouth for 9 months.	Total n=364 Participants Total of all reporting groups
Age, Continuous	43.8 years STANDARD_DEVIATION 10.78 • n=5 Participants	41.6 years STANDARD_DEVIATION 10.65 • n=7 Participants	42.7 years STANDARD_DEVIATION 10.76 • n=5 Participants
Sex: Female, Male Female	65 Participants n=5 Participants	59 Participants n=7 Participants	124 Participants n=5 Participants
Sex: Female, Male Male	117 Participants n=5 Participants	123 Participants n=7 Participants	240 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	43 Participants n=5 Participants	40 Participants n=7 Participants	83 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	138 Participants n=5 Participants	137 Participants n=7 Participants	275 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants
Baseline Urine protein to creatinine ratio (UPCR)	1.300 g/gram n=5 Participants	1.264 g/gram n=7 Participants	1.282 g/gram n=5 Participants
Baseline Estimated glomerular filtration rate (eGFR)	56.006 ml/min/1.73 m2 n=5 Participants	55.565 ml/min/1.73 m2 n=7 Participants	55.785 ml/min/1.73 m2 n=5 Participants

PRIMARY outcome

Timeframe: 9 months

Population: Full analysis set - global study - Part A

Outcome measures

Outcome measures
Measure	Nefecon n=97 Participants Nefecon 16 mg once daily by mouth for 9 months. Nefecon: Nefecon 16 mg for daily administration by mouth for 9 months.	Placebo Oral Capsule n=102 Participants Placebo oral capsule once daily by mouth for 9 months. Placebo oral capsule: Placebo capsules for daily administration by mouth for 9 months.
Part A: Ratio of Urine Protein to Creatinine Ratio (UPCR) at 9 Months Compared to Baseline	0.69 ratio Interval 0.61 to 0.79	0.95 ratio Interval 0.83 to 1.08

PRIMARY outcome

Timeframe: Up to 2 years and 1 month

Population: Full analysis set - global study - Part B

Part B Primary endpoint: Time-weighted average of estimated glomerular filtration rate (eGFR) recordings observed at each time point over 2 years. The eGFR (CKD-EPI) at 2 years (which must have been repeated to provide a second value obtained within 14 to 35 days) was the geometric mean of the 2 assessments.

Outcome measures

Outcome measures
Measure	Nefecon n=182 Participants Nefecon 16 mg once daily by mouth for 9 months. Nefecon: Nefecon 16 mg for daily administration by mouth for 9 months.	Placebo Oral Capsule n=182 Participants Placebo oral capsule once daily by mouth for 9 months. Placebo oral capsule: Placebo capsules for daily administration by mouth for 9 months.
Part B: Time-weighted Average of Estimated Glomerular Filtration Rate (eGFR)	0.96 mL/min/1.73m2 Interval 0.93 to 0.98	0.87 mL/min/1.73m2 Interval 0.84 to 0.89

SECONDARY outcome

Timeframe: 9 months

Population: Full analysis set - global study - Part A

Part A: Ratio of eGFR at 9 months compared to baseline calculated using the CKD-EPI formula.

Outcome measures

Outcome measures
Measure	Nefecon n=97 Participants Nefecon 16 mg once daily by mouth for 9 months. Nefecon: Nefecon 16 mg for daily administration by mouth for 9 months.	Placebo Oral Capsule n=102 Participants Placebo oral capsule once daily by mouth for 9 months. Placebo oral capsule: Placebo capsules for daily administration by mouth for 9 months.
Part A: Ratio of eGFR at 9 Months	1.00 mL/min/1.73m2 Interval 0.96 to 1.03	0.93 mL/min/1.73m2 Interval 0.9 to 0.96

SECONDARY outcome

Timeframe: 12 months

Population: Full analysis set - global study - Part A

Part A: Ratio of eGFR at 12 months compared to baseline calculated using the CKD-EPI formula.

Outcome measures

Outcome measures
Measure	Nefecon n=97 Participants Nefecon 16 mg once daily by mouth for 9 months. Nefecon: Nefecon 16 mg for daily administration by mouth for 9 months.	Placebo Oral Capsule n=102 Participants Placebo oral capsule once daily by mouth for 9 months. Placebo oral capsule: Placebo capsules for daily administration by mouth for 9 months.
Part A: Ratio of eGFR at 12 Months	0.97 mL/min/1.73m2 Interval 0.93 to 1.01	0.91 mL/min/1.73m2 Interval 0.88 to 0.95

SECONDARY outcome

Timeframe: 9 months

Population: Full analysis set - global study - Part A

Part A: Ratio of urine albumin to creatinine ratio (UACR) at 9 months compared to baseline.

Outcome measures

Outcome measures
Measure	Nefecon n=97 Participants Nefecon 16 mg once daily by mouth for 9 months. Nefecon: Nefecon 16 mg for daily administration by mouth for 9 months.	Placebo Oral Capsule n=102 Participants Placebo oral capsule once daily by mouth for 9 months. Placebo oral capsule: Placebo capsules for daily administration by mouth for 9 months.
Part A: Ratio of Urine Albumin to Creatinine Ratio (UACR) at 9 Months	0.64 g/gram Interval 0.55 to 0.75	0.93 g/gram Interval 0.8 to 1.09

SECONDARY outcome

Timeframe: Over 2 years

Population: Full analysis set - global study - Part B

Part B: Time to 30% reduction from baseline in eGFR (CKD-EPI) confirmed by a second value. For clarity: Please note that the number of patients with a 30% reduction is presented with statistical analysis of the time to 30% reduction.

Outcome measures

Outcome measures
Measure	Nefecon n=182 Participants Nefecon 16 mg once daily by mouth for 9 months. Nefecon: Nefecon 16 mg for daily administration by mouth for 9 months.	Placebo Oral Capsule n=182 Participants Placebo oral capsule once daily by mouth for 9 months. Placebo oral capsule: Placebo capsules for daily administration by mouth for 9 months.
Part B: Time to 30% Reduction in eGFR	21 Participants	39 Participants

SECONDARY outcome

Timeframe: Over 2 years

Population: Full analysis set - global study - Part B

Part B: Time from the first dose of study drug until receiving rescue medication. For clarity: Please note that the number of patients receiving rescue medication is presented with statistical analysis of the time to receiving rescue medication.

Outcome measures

Outcome measures
Measure	Nefecon n=182 Participants Nefecon 16 mg once daily by mouth for 9 months. Nefecon: Nefecon 16 mg for daily administration by mouth for 9 months.	Placebo Oral Capsule n=182 Participants Placebo oral capsule once daily by mouth for 9 months. Placebo oral capsule: Placebo capsules for daily administration by mouth for 9 months.
Part B: Time to Receiving Rescue Medication.	15 Participants	20 Participants

SECONDARY outcome

Timeframe: 12, 18 and 24 months

Population: Full analysis set - global study - Part B

Part B: Ratio of UPCR, UACR, and eGFR (CKD-EPI) compared to baseline averaged over time points between 12 and 24 months, inclusive, following the first dose of study drug

Outcome measures

Outcome measures
Measure	Nefecon n=172 Participants Nefecon 16 mg once daily by mouth for 9 months. Nefecon: Nefecon 16 mg for daily administration by mouth for 9 months.	Placebo Oral Capsule n=173 Participants Placebo oral capsule once daily by mouth for 9 months. Placebo oral capsule: Placebo capsules for daily administration by mouth for 9 months.
Part B: Ratio of UPCR Compared to Baseline Averaged Over Time Points Between 12 and 24 Months	0.60 g/gram Interval 0.54 to 0.66	1.01 g/gram Interval 0.91 to 1.12

SECONDARY outcome

Timeframe: 12 to 24 months

Population: Full analysis set - global study - Part B

Part B: Ratio of UPCR, UACR, and eGFR (CKD-EPI) compared to baseline averaged over time points between 12 and 24 months, inclusive, following the first dose of study drug.

Outcome measures

Outcome measures
Measure	Nefecon n=172 Participants Nefecon 16 mg once daily by mouth for 9 months. Nefecon: Nefecon 16 mg for daily administration by mouth for 9 months.	Placebo Oral Capsule n=173 Participants Placebo oral capsule once daily by mouth for 9 months. Placebo oral capsule: Placebo capsules for daily administration by mouth for 9 months.
Part B: Ratio of UACR Compared to Baseline Averaged Over Time Points Between 12 and 24 Months	0.52 g/gram Interval 0.46 to 0.58	0.96 g/gram Interval 0.86 to 1.08

SECONDARY outcome

Timeframe: 12 to 24 months

Population: Full analysis set - global study - Part B

Part B: Ratio of UPCR, UACR, and eGFR (CKD-EPI) compared to baseline averaged over time points between 12 and 24 months, inclusive, following the first dose of study drug;

Outcome measures

Outcome measures
Measure	Nefecon n=163 Participants Nefecon 16 mg once daily by mouth for 9 months. Nefecon: Nefecon 16 mg for daily administration by mouth for 9 months.	Placebo Oral Capsule n=166 Participants Placebo oral capsule once daily by mouth for 9 months. Placebo oral capsule: Placebo capsules for daily administration by mouth for 9 months.
Part B: Ratio of eGFR Compared to Baseline Averaged Over Time Points Between 12 and 24 Months	0.93 mL/min/1.73m2 Interval 0.9 to 0.96	0.84 mL/min/1.73m2 Interval 0.81 to 0.86

SECONDARY outcome

Timeframe: 12 to 24 months

Population: Full analysis set - global study - Part B

Part B: Proportion of patients without microhematuria in at least 2 of the following time points: 12, 18, and 24 months following the first dose of study drug

Outcome measures

Outcome measures
Measure	Nefecon n=182 Participants Nefecon 16 mg once daily by mouth for 9 months. Nefecon: Nefecon 16 mg for daily administration by mouth for 9 months.	Placebo Oral Capsule n=182 Participants Placebo oral capsule once daily by mouth for 9 months. Placebo oral capsule: Placebo capsules for daily administration by mouth for 9 months.
Part B: Proportion of Patients Without Microhematuria	94 Participants	59 Participants

SECONDARY outcome

Timeframe: 9 months

Population: Full analysis set - global study - Part B

Part B: Short Form 36 (SF-36) quality of life assessment at 9 and 24 months. The 36-Item Short Form Health Survey (SF-36) is a set of generic, coherent, and easily administered quality-of-life measures. These measures rely upon patient self-reporting and have been widely used. It consists of eight health concepts: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. Higher scores indicate better health. Scores represent the percentage of total possible score achieved.

Outcome measures

Outcome measures
Measure	Nefecon n=170 Participants Nefecon 16 mg once daily by mouth for 9 months. Nefecon: Nefecon 16 mg for daily administration by mouth for 9 months.	Placebo Oral Capsule n=170 Participants Placebo oral capsule once daily by mouth for 9 months. Placebo oral capsule: Placebo capsules for daily administration by mouth for 9 months.
Part B: Short Form 36 (SF-36) Quality of Life Assessment at 9 Months. Physical Functioning	52.722 Percentage of total possible score Standard Deviation 6.7370	54.276 Percentage of total possible score Standard Deviation 5.2243
Part B: Short Form 36 (SF-36) Quality of Life Assessment at 9 Months. Social Function	50.941 Percentage of total possible score Standard Deviation 8.3606	51.707 Percentage of total possible score Standard Deviation 7.9259
Part B: Short Form 36 (SF-36) Quality of Life Assessment at 9 Months. Role Emotional	49.574 Percentage of total possible score Standard Deviation 9.4322	50.393 Percentage of total possible score Standard Deviation 8.3001
Part B: Short Form 36 (SF-36) Quality of Life Assessment at 9 Months. Role Physical	51.028 Percentage of total possible score Standard Deviation 8.0207	52.693 Percentage of total possible score Standard Deviation 6.6600
Part B: Short Form 36 (SF-36) Quality of Life Assessment at 9 Months. Vitality	51.826 Percentage of total possible score Standard Deviation 10.0909	53.490 Percentage of total possible score Standard Deviation 9.3987
Part B: Short Form 36 (SF-36) Quality of Life Assessment at 9 Months. Bodily Pain	54.353 Percentage of total possible score Standard Deviation 9.0306	54.659 Percentage of total possible score Standard Deviation 9.2387
Part B: Short Form 36 (SF-36) Quality of Life Assessment at 9 Months. General Health	47.058 Percentage of total possible score Standard Deviation 9.6373	48.014 Percentage of total possible score Standard Deviation 10.0120
Part B: Short Form 36 (SF-36) Quality of Life Assessment at 9 Months. Mental Component Summary	49.564 Percentage of total possible score Standard Deviation 9.2834	49.760 Percentage of total possible score Standard Deviation 8.8974
Part B: Short Form 36 (SF-36) Quality of Life Assessment at 9 Months. Mental Health	50.226 Percentage of total possible score Standard Deviation 8.9539	50.099 Percentage of total possible score Standard Deviation 8.8483
Part B: Short Form 36 (SF-36) Quality of Life Assessment at 9 Months. Physical Component Summary	52.257 Percentage of total possible score Standard Deviation 7.2188	53.732 Percentage of total possible score Standard Deviation 6.5876

SECONDARY outcome

Timeframe: 24 months

Population: Full analysis set - global study - Part B

Outcome measures

Outcome measures
Measure	Nefecon n=159 Participants Nefecon 16 mg once daily by mouth for 9 months. Nefecon: Nefecon 16 mg for daily administration by mouth for 9 months.	Placebo Oral Capsule n=164 Participants Placebo oral capsule once daily by mouth for 9 months. Placebo oral capsule: Placebo capsules for daily administration by mouth for 9 months.
Part B: Short Form 36 (SF-36) Quality of Life Assessment at 24 Months. Role Emotional	50.322 Percentage of total possible score Standard Deviation 8.4690	49.333 Percentage of total possible score Standard Deviation 10.0789
Part B: Short Form 36 (SF-36) Quality of Life Assessment at 24 Months. Vitality	53.291 Percentage of total possible score Standard Deviation 8.8558	52.364 Percentage of total possible score Standard Deviation 10.0023
Part B: Short Form 36 (SF-36) Quality of Life Assessment at 24 Months. Bodily Pain	53.385 Percentage of total possible score Standard Deviation 9.6352	53.208 Percentage of total possible score Standard Deviation 9.9811
Part B: Short Form 36 (SF-36) Quality of Life Assessment at 24 Months. General Health	47.038 Percentage of total possible score Standard Deviation 9.3450	47.214 Percentage of total possible score Standard Deviation 9.9564
Part B: Short Form 36 (SF-36) Quality of Life Assessment at 24 Months. Mental Component Summary	51.246 Percentage of total possible score Standard Deviation 8.1362	49.743 Percentage of total possible score Standard Deviation 10.2184
Part B: Short Form 36 (SF-36) Quality of Life Assessment at 24 Months. Mental Health	51.691 Percentage of total possible score Standard Deviation 8.2104	50.294 Percentage of total possible score Standard Deviation 10.0007
Part B: Short Form 36 (SF-36) Quality of Life Assessment at 24 Months. Physical Component Summary	51.443 Percentage of total possible score Standard Deviation 7.5200	51.993 Percentage of total possible score Standard Deviation 7.1783
Part B: Short Form 36 (SF-36) Quality of Life Assessment at 24 Months. Physical Functioning	52.665 Percentage of total possible score Standard Deviation 7.6364	53.059 Percentage of total possible score Standard Deviation 6.9006
Part B: Short Form 36 (SF-36) Quality of Life Assessment at 24 Months. Role Physical	50.948 Percentage of total possible score Standard Deviation 7.8921	50.722 Percentage of total possible score Standard Deviation 8.8255
Part B: Short Form 36 (SF-36) Quality of Life Assessment at 24 Months. Social Function	51.949 Percentage of total possible score Standard Deviation 7.9677	51.471 Percentage of total possible score Standard Deviation 8.9304

Adverse Events

Nefecon

Serious events: 18 serious events

Other events: 108 other events

Deaths: 1 deaths

Placebo Oral Capsule

Serious events: 9 serious events

Other events: 69 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Program Leader

Calliditas Therapeutics

Phone: 0737456451

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Nefecon n=182 participants at risk Nefecon 16 mg once daily by mouth for 9 months. Nefecon: Nefecon 16 mg for daily administration by mouth for 9 months.	Placebo Oral Capsule n=182 participants at risk Placebo oral capsule once daily by mouth for 9 months. Placebo oral capsule: Placebo capsules for daily administration by mouth for 9 months.
General disorders Edema peripheral	15.4% 28/182 • AEs were recorded from time of first dose of study treatment until 2 years after first dose (end of study). Treatment emergent AEs were those that occurred after the first dose of study drug until 14 days after the last dose, including tapering. SAEs were recorded from time of patient informed consent until end of study, i.e until 2 years and 3 months (including follow-up period) Treatment emergent SAEs are listed on Clinicaltrial.gov.	3.8% 7/182 • AEs were recorded from time of first dose of study treatment until 2 years after first dose (end of study). Treatment emergent AEs were those that occurred after the first dose of study drug until 14 days after the last dose, including tapering. SAEs were recorded from time of patient informed consent until end of study, i.e until 2 years and 3 months (including follow-up period) Treatment emergent SAEs are listed on Clinicaltrial.gov.
Vascular disorders Hypertension	11.5% 21/182 • AEs were recorded from time of first dose of study treatment until 2 years after first dose (end of study). Treatment emergent AEs were those that occurred after the first dose of study drug until 14 days after the last dose, including tapering. SAEs were recorded from time of patient informed consent until end of study, i.e until 2 years and 3 months (including follow-up period) Treatment emergent SAEs are listed on Clinicaltrial.gov.	3.3% 6/182 • AEs were recorded from time of first dose of study treatment until 2 years after first dose (end of study). Treatment emergent AEs were those that occurred after the first dose of study drug until 14 days after the last dose, including tapering. SAEs were recorded from time of patient informed consent until end of study, i.e until 2 years and 3 months (including follow-up period) Treatment emergent SAEs are listed on Clinicaltrial.gov.
Musculoskeletal and connective tissue disorders Muscle spasms	12.1% 22/182 • AEs were recorded from time of first dose of study treatment until 2 years after first dose (end of study). Treatment emergent AEs were those that occurred after the first dose of study drug until 14 days after the last dose, including tapering. SAEs were recorded from time of patient informed consent until end of study, i.e until 2 years and 3 months (including follow-up period) Treatment emergent SAEs are listed on Clinicaltrial.gov.	3.8% 7/182 • AEs were recorded from time of first dose of study treatment until 2 years after first dose (end of study). Treatment emergent AEs were those that occurred after the first dose of study drug until 14 days after the last dose, including tapering. SAEs were recorded from time of patient informed consent until end of study, i.e until 2 years and 3 months (including follow-up period) Treatment emergent SAEs are listed on Clinicaltrial.gov.
Skin and subcutaneous tissue disorders Acne	11.0% 20/182 • AEs were recorded from time of first dose of study treatment until 2 years after first dose (end of study). Treatment emergent AEs were those that occurred after the first dose of study drug until 14 days after the last dose, including tapering. SAEs were recorded from time of patient informed consent until end of study, i.e until 2 years and 3 months (including follow-up period) Treatment emergent SAEs are listed on Clinicaltrial.gov.	1.1% 2/182 • AEs were recorded from time of first dose of study treatment until 2 years after first dose (end of study). Treatment emergent AEs were those that occurred after the first dose of study drug until 14 days after the last dose, including tapering. SAEs were recorded from time of patient informed consent until end of study, i.e until 2 years and 3 months (including follow-up period) Treatment emergent SAEs are listed on Clinicaltrial.gov.
Infections and infestations Nasopharyngitis	9.3% 17/182 • AEs were recorded from time of first dose of study treatment until 2 years after first dose (end of study). Treatment emergent AEs were those that occurred after the first dose of study drug until 14 days after the last dose, including tapering. SAEs were recorded from time of patient informed consent until end of study, i.e until 2 years and 3 months (including follow-up period) Treatment emergent SAEs are listed on Clinicaltrial.gov.	10.4% 19/182 • AEs were recorded from time of first dose of study treatment until 2 years after first dose (end of study). Treatment emergent AEs were those that occurred after the first dose of study drug until 14 days after the last dose, including tapering. SAEs were recorded from time of patient informed consent until end of study, i.e until 2 years and 3 months (including follow-up period) Treatment emergent SAEs are listed on Clinicaltrial.gov.
General disorders Headache	10.4% 19/182 • AEs were recorded from time of first dose of study treatment until 2 years after first dose (end of study). Treatment emergent AEs were those that occurred after the first dose of study drug until 14 days after the last dose, including tapering. SAEs were recorded from time of patient informed consent until end of study, i.e until 2 years and 3 months (including follow-up period) Treatment emergent SAEs are listed on Clinicaltrial.gov.	7.7% 14/182 • AEs were recorded from time of first dose of study treatment until 2 years after first dose (end of study). Treatment emergent AEs were those that occurred after the first dose of study drug until 14 days after the last dose, including tapering. SAEs were recorded from time of patient informed consent until end of study, i.e until 2 years and 3 months (including follow-up period) Treatment emergent SAEs are listed on Clinicaltrial.gov.
Infections and infestations Upper respiratory tract infection	5.5% 10/182 • AEs were recorded from time of first dose of study treatment until 2 years after first dose (end of study). Treatment emergent AEs were those that occurred after the first dose of study drug until 14 days after the last dose, including tapering. SAEs were recorded from time of patient informed consent until end of study, i.e until 2 years and 3 months (including follow-up period) Treatment emergent SAEs are listed on Clinicaltrial.gov.	5.5% 10/182 • AEs were recorded from time of first dose of study treatment until 2 years after first dose (end of study). Treatment emergent AEs were those that occurred after the first dose of study drug until 14 days after the last dose, including tapering. SAEs were recorded from time of patient informed consent until end of study, i.e until 2 years and 3 months (including follow-up period) Treatment emergent SAEs are listed on Clinicaltrial.gov.
Gastrointestinal disorders Dyspepsia	7.1% 13/182 • AEs were recorded from time of first dose of study treatment until 2 years after first dose (end of study). Treatment emergent AEs were those that occurred after the first dose of study drug until 14 days after the last dose, including tapering. SAEs were recorded from time of patient informed consent until end of study, i.e until 2 years and 3 months (including follow-up period) Treatment emergent SAEs are listed on Clinicaltrial.gov.	2.2% 4/182 • AEs were recorded from time of first dose of study treatment until 2 years after first dose (end of study). Treatment emergent AEs were those that occurred after the first dose of study drug until 14 days after the last dose, including tapering. SAEs were recorded from time of patient informed consent until end of study, i.e until 2 years and 3 months (including follow-up period) Treatment emergent SAEs are listed on Clinicaltrial.gov.
General disorders Weight increased	5.5% 10/182 • AEs were recorded from time of first dose of study treatment until 2 years after first dose (end of study). Treatment emergent AEs were those that occurred after the first dose of study drug until 14 days after the last dose, including tapering. SAEs were recorded from time of patient informed consent until end of study, i.e until 2 years and 3 months (including follow-up period) Treatment emergent SAEs are listed on Clinicaltrial.gov.	2.7% 5/182 • AEs were recorded from time of first dose of study treatment until 2 years after first dose (end of study). Treatment emergent AEs were those that occurred after the first dose of study drug until 14 days after the last dose, including tapering. SAEs were recorded from time of patient informed consent until end of study, i.e until 2 years and 3 months (including follow-up period) Treatment emergent SAEs are listed on Clinicaltrial.gov.
Musculoskeletal and connective tissue disorders Arthralgia	6.6% 12/182 • AEs were recorded from time of first dose of study treatment until 2 years after first dose (end of study). Treatment emergent AEs were those that occurred after the first dose of study drug until 14 days after the last dose, including tapering. SAEs were recorded from time of patient informed consent until end of study, i.e until 2 years and 3 months (including follow-up period) Treatment emergent SAEs are listed on Clinicaltrial.gov.	2.2% 4/182 • AEs were recorded from time of first dose of study treatment until 2 years after first dose (end of study). Treatment emergent AEs were those that occurred after the first dose of study drug until 14 days after the last dose, including tapering. SAEs were recorded from time of patient informed consent until end of study, i.e until 2 years and 3 months (including follow-up period) Treatment emergent SAEs are listed on Clinicaltrial.gov.
Psychiatric disorders Insomnia	5.5% 10/182 • AEs were recorded from time of first dose of study treatment until 2 years after first dose (end of study). Treatment emergent AEs were those that occurred after the first dose of study drug until 14 days after the last dose, including tapering. SAEs were recorded from time of patient informed consent until end of study, i.e until 2 years and 3 months (including follow-up period) Treatment emergent SAEs are listed on Clinicaltrial.gov.	3.8% 7/182 • AEs were recorded from time of first dose of study treatment until 2 years after first dose (end of study). Treatment emergent AEs were those that occurred after the first dose of study drug until 14 days after the last dose, including tapering. SAEs were recorded from time of patient informed consent until end of study, i.e until 2 years and 3 months (including follow-up period) Treatment emergent SAEs are listed on Clinicaltrial.gov.
General disorders Fatigue	5.5% 10/182 • AEs were recorded from time of first dose of study treatment until 2 years after first dose (end of study). Treatment emergent AEs were those that occurred after the first dose of study drug until 14 days after the last dose, including tapering. SAEs were recorded from time of patient informed consent until end of study, i.e until 2 years and 3 months (including follow-up period) Treatment emergent SAEs are listed on Clinicaltrial.gov.	3.8% 7/182 • AEs were recorded from time of first dose of study treatment until 2 years after first dose (end of study). Treatment emergent AEs were those that occurred after the first dose of study drug until 14 days after the last dose, including tapering. SAEs were recorded from time of patient informed consent until end of study, i.e until 2 years and 3 months (including follow-up period) Treatment emergent SAEs are listed on Clinicaltrial.gov.
Gastrointestinal disorders Diarrhea	4.9% 9/182 • AEs were recorded from time of first dose of study treatment until 2 years after first dose (end of study). Treatment emergent AEs were those that occurred after the first dose of study drug until 14 days after the last dose, including tapering. SAEs were recorded from time of patient informed consent until end of study, i.e until 2 years and 3 months (including follow-up period) Treatment emergent SAEs are listed on Clinicaltrial.gov.	5.5% 10/182 • AEs were recorded from time of first dose of study treatment until 2 years after first dose (end of study). Treatment emergent AEs were those that occurred after the first dose of study drug until 14 days after the last dose, including tapering. SAEs were recorded from time of patient informed consent until end of study, i.e until 2 years and 3 months (including follow-up period) Treatment emergent SAEs are listed on Clinicaltrial.gov.
Skin and subcutaneous tissue disorders Rash	5.5% 10/182 • AEs were recorded from time of first dose of study treatment until 2 years after first dose (end of study). Treatment emergent AEs were those that occurred after the first dose of study drug until 14 days after the last dose, including tapering. SAEs were recorded from time of patient informed consent until end of study, i.e until 2 years and 3 months (including follow-up period) Treatment emergent SAEs are listed on Clinicaltrial.gov.	3.8% 7/182 • AEs were recorded from time of first dose of study treatment until 2 years after first dose (end of study). Treatment emergent AEs were those that occurred after the first dose of study drug until 14 days after the last dose, including tapering. SAEs were recorded from time of patient informed consent until end of study, i.e until 2 years and 3 months (including follow-up period) Treatment emergent SAEs are listed on Clinicaltrial.gov.
Gastrointestinal disorders Nausea	4.4% 8/182 • AEs were recorded from time of first dose of study treatment until 2 years after first dose (end of study). Treatment emergent AEs were those that occurred after the first dose of study drug until 14 days after the last dose, including tapering. SAEs were recorded from time of patient informed consent until end of study, i.e until 2 years and 3 months (including follow-up period) Treatment emergent SAEs are listed on Clinicaltrial.gov.	6.6% 12/182 • AEs were recorded from time of first dose of study treatment until 2 years after first dose (end of study). Treatment emergent AEs were those that occurred after the first dose of study drug until 14 days after the last dose, including tapering. SAEs were recorded from time of patient informed consent until end of study, i.e until 2 years and 3 months (including follow-up period) Treatment emergent SAEs are listed on Clinicaltrial.gov.