Trial Outcomes & Findings for Acthar for Treatment of Proteinuria in Membranous Nephropathy Patients (NCT NCT01386554)

Last Updated: 2019-11-20

Results Overview

The participant's response was considered the average of the two PCR values from the 24-hour urine collected at Visit 8 (Week 24). Urine protein creatinine ratio (uPCR) was used to assess remission (partial and complete). Complete remission = uPCR \< 0.3 g/g; partial remission = uPCR \< 50% of baseline uPCR and \> 0.3 g/g but \< 3.0 g/g.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

60 participants

Primary outcome timeframe

At Visit 8 (Week 24)

Results posted on

2019-11-20

Participant Flow

Participants were enrolled at study sites in United Staes. The first participant was screened on 20 October 2011. The last study visit occurred on 05 May 2017.

132 participants were screened.

Participant milestones

Participant milestones
Measure	Acthar 40U 40 units (U) of Acthar administered 5 times a week	Acthar 80U 80 U of Acthar administered 2 times a week	Combined Placebo Placebo (volume matched for 40 U or 80 U) administered 5 times (40 U) or 2 times (80 U) per week
Overall Study STARTED	4	35	21
Overall Study COMPLETED	1	26	15
Overall Study NOT COMPLETED	3	9	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Acthar 40U 40 units (U) of Acthar administered 5 times a week	Acthar 80U 80 U of Acthar administered 2 times a week	Combined Placebo Placebo (volume matched for 40 U or 80 U) administered 5 times (40 U) or 2 times (80 U) per week
Overall Study Lost to Follow-up	0	0	1
Overall Study Adverse Event	2	5	2
Overall Study Progressive disease	1	2	2
Overall Study Administration of live vaccines	0	1	0
Overall Study Investigator discretion	0	0	1
Overall Study Reason not collected	0	1	0

Baseline Characteristics

Acthar for Treatment of Proteinuria in Membranous Nephropathy Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Acthar 40U n=4 Participants 40 U of Acthar administered 5 times a week	Acthar 80U n=35 Participants 80 U of Acthar administered 2 times a week	Combined Placbeo n=21 Participants Placebo (volume matched for 40 U or 80 U) administered 5 times (40 U) or 2 times (80 U) per week	Total n=60 Participants Total of all reporting groups
Age, Continuous	55.0 Years STANDARD_DEVIATION 5.72 • n=5 Participants	49.9 Years STANDARD_DEVIATION 13.18 • n=7 Participants	45.4 Years STANDARD_DEVIATION 12.24 • n=5 Participants	48.7 Years STANDARD_DEVIATION 12.65 • n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	9 Participants n=7 Participants	4 Participants n=5 Participants	15 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	26 Participants n=7 Participants	17 Participants n=5 Participants	45 Participants n=4 Participants
Region of Enrollment Canada	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Region of Enrollment Turkey	0 Participants n=5 Participants	6 Participants n=7 Participants	4 Participants n=5 Participants	10 Participants n=4 Participants
Region of Enrollment United States	3 Participants n=5 Participants	15 Participants n=7 Participants	10 Participants n=5 Participants	28 Participants n=4 Participants
Region of Enrollment Mexico	0 Participants n=5 Participants	4 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Region of Enrollment Chile	0 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Region of Enrollment Argentina	0 Participants n=5 Participants	6 Participants n=7 Participants	2 Participants n=5 Participants	8 Participants n=4 Participants
Region of Enrollment Colombia	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants

PRIMARY outcome

Timeframe: At Visit 8 (Week 24)

Population: ITT Population included all randomized participants who received ≥ 1 dose of study mediation and who contributed any efficacy data in the study.

Outcome measures

Outcome measures
Measure	Acthar 40U n=4 Participants 40 U of Acthar administered 5 times a week	Acthar 80U n=35 Participants 80 U of Acthar administered 2 times a week	Combined Placebo n=21 Participants Placebo (volume matched for 40 U or 80 U) administered 5 times (40 U) or 2 times (80 U) per week
Percentage of Participants With Complete or Partial Remission in Proteinuria at 24 Weeks Partial remission in proteinuria	1 Participants	5 Participants	2 Participants
Percentage of Participants With Complete or Partial Remission in Proteinuria at 24 Weeks Complete remission in proteinuria	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: At Visit 9 (Week 28)

Population: ITT Population

The participant's response was considered the average of the two PCR values from the 24-hour urine collections at Visit 8 (Week 24).

Outcome measures

Outcome measures
Measure	Acthar 40U n=4 Participants 40 U of Acthar administered 5 times a week	Acthar 80U n=35 Participants 80 U of Acthar administered 2 times a week	Combined Placebo n=21 Participants Placebo (volume matched for 40 U or 80 U) administered 5 times (40 U) or 2 times (80 U) per week
Percentage of Participants With Sustained Remission	1 Participants	4 Participants	2 Participants

Adverse Events

Acthar 40U

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Acthar 80U

Serious events: 7 serious events

Other events: 31 other events

Deaths: 0 deaths

Combined Placebo

Serious events: 3 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Information Call Center

Mallinckrodt Pharmaceuticals

Phone: 800-556-3314

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Institution/Investigator shall not, without Sponsor's prior written consent, independently publish or otherwise disclose any results of the study until a Multi-Center Publication is published. If a Multi-Center Publication is not submitted for publication within the specified timeframe, Institution and Principal Investigator shall have the right to publish and present the results of Institution's and Principal Investigator's activities solely in accordance with the Sponsor's written provisions.
Publication restrictions are in place

Restriction type: OTHER

Measure	Acthar 40U n=4 participants at risk 40 U of Acthar administered 5 times a week	Acthar 80U n=35 participants at risk 80 U of Acthar administered 2 times a week	Combined Placebo n=21 participants at risk Placebo (volume matched for 40 U or 80 U) administered 5 times (40 U) or 2 times (80 U) per week
Renal and urinary disorders Nephrotic syndrome	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	4.8% 1/21 • Number of events 1 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Vascular disorders Hypertension	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	4.8% 1/21 • Number of events 1 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Renal and urinary disorders Renal impairment	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	4.8% 1/21 • Number of events 1 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	2.9% 1/35 • Number of events 1 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Immune system disorders Drug hypersensitivity	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	2.9% 1/35 • Number of events 1 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Renal and urinary disorders Renal failure acute	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	5.7% 2/35 • Number of events 2 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Infections and infestations Pneumonia	25.0% 1/4 • Number of events 1 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	2.9% 1/35 • Number of events 1 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder transitional cell carcinoma	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	2.9% 1/35 • Number of events 1 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Vascular disorders Deep vein thrombosis	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	2.9% 1/35 • Number of events 1 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
General disorders Generalized edema	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	2.9% 1/35 • Number of events 1 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Gastrointestinal disorders Peritonitis	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	2.9% 1/35 • Number of events 1 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Renal and urinary disorders Renal failure chronic	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	2.9% 1/35 • Number of events 1 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Metabolism and nutrition disorders Hypokalemia	25.0% 1/4 • Number of events 1 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Metabolism and nutrition disorders Hypomagnesemia	25.0% 1/4 • Number of events 1 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Metabolism and nutrition disorders Diabetes mellitus	25.0% 1/4 • Number of events 1 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.

Measure	Acthar 40U n=4 participants at risk 40 U of Acthar administered 5 times a week	Acthar 80U n=35 participants at risk 80 U of Acthar administered 2 times a week	Combined Placebo n=21 participants at risk Placebo (volume matched for 40 U or 80 U) administered 5 times (40 U) or 2 times (80 U) per week
Infections and infestations Upper respiratory tract infection	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	5.7% 2/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	23.8% 5/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Infections and infestations Gastroenteritis	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	5.7% 2/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	9.5% 2/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Infections and infestations Urinary tract infection	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	5.7% 2/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	4.8% 1/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Infections and infestations Nasopharyngitis	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	5.7% 2/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	4.8% 1/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Infections and infestations Sinusitis	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	5.7% 2/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	4.8% 1/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Infections and infestations Bronchitis	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	5.7% 2/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Infections and infestations Respiratory infection	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	9.5% 2/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
General disorders Edema peripheral	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	31.4% 11/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	19.0% 4/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
General disorders Fatigue	25.0% 1/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	5.7% 2/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	9.5% 2/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
General disorders Asthenia	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	5.7% 2/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
General disorders Edema	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	5.7% 2/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Gastrointestinal disorders Diarrhea	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	14.3% 5/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	9.5% 2/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Gastrointestinal disorders Nausea	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	11.4% 4/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	4.8% 1/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Gastrointestinal disorders Dyspepsia	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	11.4% 4/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Gastrointestinal disorders Abdominal distension	25.0% 1/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	2.9% 1/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Gastrointestinal disorders Flatulence	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	5.7% 2/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Gastrointestinal disorders Odynophagia	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	5.7% 2/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Gastrointestinal disorders Feces discolored	25.0% 1/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Nervous system disorders Dizziness	25.0% 1/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	14.3% 5/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	4.8% 1/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Nervous system disorders Headache	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	8.6% 3/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	14.3% 3/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Nervous system disorders Dysgeusia	25.0% 1/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	4.8% 1/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Investigations Blood creatine phosphokinase increased	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	5.7% 2/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	9.5% 2/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Investigations Weight increased	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	2.9% 1/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	14.3% 3/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Investigations Neutrophil count increased	25.0% 1/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	14.3% 5/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	9.5% 2/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Musculoskeletal and connective tissue disorders Muscle spasms	25.0% 1/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	5.7% 2/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	4.8% 1/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Musculoskeletal and connective tissue disorders Muscular weakness	25.0% 1/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	11.4% 4/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Metabolism and nutrition disorders Increased appetite	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	5.7% 2/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Skin and subcutaneous tissue disorders Skin discoloration	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	5.7% 2/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Skin and subcutaneous tissue disorders Acne	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	5.7% 2/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Renal and urinary disorders Chromaturia	25.0% 1/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Renal and urinary disorders Pollakiuria	25.0% 1/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Psychiatric disorders Insomnia	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	14.3% 5/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Psychiatric disorders Mood swings	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	5.7% 2/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	2.9% 1/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	9.5% 2/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	2.9% 1/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	9.5% 2/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Blood and lymphatic system disorders Amemia	25.0% 1/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	5.7% 2/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/4 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	5.7% 2/35 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.	0.00% 0/21 • Week 24 plus 30 days Safety population included all randomized participants who received ≥ 1 dose of study medication.