A Proof of Concept Study for a 12 Month Treatment in Patients With C3G or IC-MPGN Treated With ACH-0144471

• Sponsor: Alexion Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03459443
• Collaborator: (none)
• Enrollment: 22
• Locations: 13
• Arm: 1
• Actual Duration (Months): 33.3
• Patients Per Site: 1.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The primary purpose of this study was to evaluate the efficacy of 12 months of oral ACH-0144471 (also known as danicopan and ALXN2040) in participants with C3G or IC-MPGN based on histologic scoring and proteinuria.

Condition or Disease	Intervention/Treatment	Phase
C3 Glomerulonephritis; C3 Glomerulopathy; Immune Complex Membranoproliferative Glomerulonephritis; IC-MPGN; Dense Deposit Disease	Drug: Danicopan	Phase 2

Detailed Description

This was an open-label study to evaluate the efficacy of treatment with danicopan in participants 12 years of age or older with biopsy-confirmed C3G or IC-MPGN who had not undergone renal transplantation. All participants were to receive active treatment with danicopan for approximately 40 months. The starting dosage was to be 100 mg TID, and after 2 weeks, the dosage was to be increased to 200 mg TID for participants with body weight ≥ 60 kg or 150 mg TID for participants with body weight < 60 kg. Planned enrollment was approximately 20 participants.

Study Design

• Study Type: Interventional
• Actual Enrollment: 22 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Phase 2 Proof-of-Concept Study in Patients With C3 Glomerulopathy (C3G) or Immune-Complex Membranoproliferative Glomerulonephritis (IC-MPGN) Treated With ACH-0144471
• Actual Study Start Date: Jun 20, 2018
• Actual Primary Completion Date: Mar 29, 2021
• Actual Study Completion Date: Mar 29, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Danicopan Danicopan was to be administered to participants with C3G or IC-MPGN at a starting dose of 100 milligrams (mg) 3 times daily (TID) for the first 2 weeks, then the dosage was to be increased to 200 mg TID for the remainder of the study.	Drug: Danicopan; Danicopan was to be administered as an oral tablet.; Other Names: ACH-4471 ACH4471 4471 ALXN2040

Outcome Measures

Primary Outcome Measures

1. Change From Baseline In Composite Biopsy Score At End Of Initial 12-Month Treatment Period [Baseline, end of initial 12-Month Treatment Period]

   The composite biopsy score was based on a score incorporating changes in the activity index, glomerular C3c staining, and glomerular macrophage infiltration at the end of the initial 12 months of treatment. The composite renal biopsy index scoring system ranged from 0 to 21, with higher scores indicating worse outcomes.

2. Participants With Reduction In Proteinuria At End Of Initial 12-Month Treatment Period [Baseline, end of initial 12-Month Treatment Period]

   Proteinuria reduction was defined as ≥30% decrease from baseline based on 24-hour urine protein (mg/day).

Secondary Outcome Measures

1. Change From Baseline In Proteinuria At End Of Initial 12-Month Treatment Period [Baseline, end of initial 12-Month Treatment Period]

   Proteinuria was assessed based on 24-hour urine collections at baseline and end of the initial 12-month Treatment Period.

2. Percent Change From Baseline In Proteinuria At End Of Initial 12-Month Treatment Period [Baseline, end of initial 12-Month Treatment Period]

   Proteinuria was assessed based on 24-hour urine collections at baseline and end of initial 12-month Treatment Period.

3. Slope Of Estimated Glomerular Filtration Rate (eGFR) From Baseline To End Of Initial 12-Month Treatment Period [End of initial 12-Month Treatment Period]

   Slope of eGFR was estimated using a simple linear regression for each participant, including all data values from baseline until the end of the Initial 12-Month Treatment Period, with eGFR as the dependent variable and time as the independent variable.

4. Change From Baseline In eGFR At End Of Initial 12-Month Treatment Period [Baseline, end of initial 12-Month Treatment Period]

   Change from baseline in eGFR at end of initial 12-Month Treatment Period is presented.

5. Participants With Significant Improvement In eGFR Relative To Baseline At End Of Initial 12-Month Treatment Period [Baseline, end of initial 12-Month Treatment Period]

   Significant improvement relative to baseline was defined as a ≥ 25% increase from baseline in eGFR.

6. Change From Baseline in eGFR Over 12 Months of Treatment For Participants Meeting eGFR Inclusion Criteria [End of initial 12-Month Treatment Period]

   Participants were eligible for enrollment if inclusion criteria were met including having an eGFR >=30 milliliters (mL)/minute (min)/1.73 square meter (m^2) at the time of screening or at any time over the preceding 4 weeks. This Outcome Measure was registered in case there were participants who were enrolled and ended up not meeting the Eligibility Criteria and was intended to report data for change from baseline in eGFR for only the participants who met the eligibility criteria (that is, participants who did not meet the eligibility criteria would have been excluded from analysis for this Outcome Measure). Since all enrolled participants met the Eligibility Criteria, none of the participants were excluded from this analysis. Therefore, this data is the same data that is presented in Outcome Measure #6 "Change From Baseline In eGFR At End Of Initial 12-Month Treatment Period". Change from baseline in eGFR at end of initial 12-Month Treatment Period is presented.

7. Change From Baseline In Measured GFR At The End Of The Initial 12-Month Treatment Period [End of initial 12-Month Treatment Period]

   Data for this Outcome Measure was to be collected where available. None of the sites collected data for this Outcome Measure.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

1. At least 12 years of age

2. Completion of the ACH471-201 clinical study OR diagnosed with biopsy-confirmed primary C3G or IC-MPGN

3. If a pre-treatment biopsy is obtained, or if a historical biopsy is available for review, it must have no more than 50% global fibrosis and no more than 50% of glomeruli with cellular crescents

4. Clinical evidence of ongoing disease based on significant proteinuria (defined as ≥500 mg/day of protein in a 24-hour urine) attributable to C3G disease or IC-MPGN in the opinion of the principal investigator (PI), and present prior to study entry and confirmed during Screening

5. If on corticosteroids, anti-hypertensive medications, anti-proteinuric medications (for example, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers), or mycophenolate mofetil, must be on a stable dose for at least 2 weeks prior to screening

6. Female participants must use an acceptable method birth control to prevent pregnancy during the clinical study and for 30 days after the last dose of study medication

7. Male participants must use highly effective birth control with a female partner to prevent pregnancy during the clinical study and for 90 days after the last dose of study medication

8. Must be up-to-date on routine vaccinations, or willing to be brought up-to-date, based on local guidelines

9. Must have access to emergency medical care

Key Exclusion Criteria

1. Have a history of a major organ transplant (for example, heart, lung, kidney, or liver) or hematopoietic stem cell/marrow transplant

2. Have a history or presence of any clinically relevant co-morbidities that would make the participant inappropriate for the study (for example, a comorbidity that is likely to result in deterioration of the participant's condition, affect the participant's safety during the study, or confound the results of the study), in the opinion of the PI

3. Have an eGFR <30 milliliter/minute/1.73 m^2 at the time of screening or at any time over the preceding 4 weeks

4. Is a renal transplant recipient or receiving renal replacement therapy

5. Have other renal diseases that would interfere with the interpretation of the study

6. Have evidence of monoclonal gammopathy of unclear significance, infections, malignancy, autoimmune diseases, or other conditions to which C3G or IC-MPGN is secondary

7. Have been diagnosed with or show evidence of hepatobiliary cholestasis

8. Females who are pregnant, nursing, or planning to become pregnant during the study or within 90 days of ACH-0144471 administration or participants with a female partner who is pregnant, nursing, or planning to become pregnant during the study or within 90 days of ACH-0144471 administration

9. Have a history of febrile illness, a body temperature >38°Celsius, or other evidence of a clinically significant active infection, within 14 days prior to danicopan administration

10. Have evidence of human immunodeficiency virus, hepatitis B infection, or active hepatitis C infection at Screening

11. Have a history of meningococcal infection within the prior year

12. Have a history of hypersensitivity reactions to commonly used antibacterial agents, including beta-lactams, penicillin, aminopenicillins, fluoroquinolones, cephalosporins, and carbapenems, which, in the opinion of the investigator and/or an appropriately qualified immunology or infectious disease expert, would make it difficult to properly provide either empiric antibiotic therapy or treat an active infection.

13. Have participated in a clinical study in which an investigational drug was given within 30 days, or within 5 half-lives of the investigational drug, whichever is longer, prior to the first dose of ACH-0144471

14. Have received eculizumab at any dose or interval within the past 50 days prior to the first dose of ACH-0144471

15. Have received tacrolimus or cyclosporine within 2 weeks of the first dose of ACH-0144471

16. Have a 12-lead electrocardiogram (ECG) with a QT interval Fridericia correction formula >450 millisecond (msec) for males or >470 msec for females, or have ECG findings which, in the opinion of the PI, could put the participant at undue risk

17. Have received any drug known to prolong the corrected QT interval within 2 weeks of the first dose of ACH-0144471 and which, in the opinion of the PI, could put the participant at undue risk

18. Have any of the following laboratory abnormalities at screening:

• Alanine transaminase > upper limit of normal (ULN)

• Aspartate aminotransferase > ULN

• Absolute neutrophil counts <1,000/microliter

• Total bilirubin >1.5* ULN

• Indirect bilirubin > ULN

• Any laboratory abnormality that, in the opinion of the PI, would make the participant inappropriate for the study

1. Unwilling or unable to comply with the study protocol for any reason

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Study Site	Birmingham	Alabama	United States	35294
2	Clinical Study Site	Stanford	California	United States	94305
3	Clinical Study Site	New Haven	Connecticut	United States	06511
4	Clinical Study Site	Cincinnati	Ohio	United States	45221
5	Clinical Study Site	Columbus	Ohio	United States	43210
6	Clinical Study Site	Philadelphia	Pennsylvania	United States	19104
7	Clinical Study Site	Sydney	New South Wales	Australia
8	Clinical Study Site	Brisbane	Queensland	Australia
9	Clinical Study Site	Melbourne	Victoria	Australia
10	Clinical Study Site	Antwerpen		Belgium
11	Clinical Study Site	Ranica		Italy
12	Clinical Study Site	Leiden		Netherlands
13	Clinical Study Site	Nijmegen		Netherlands

Sponsors and Collaborators

• Alexion Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - May 15, 2020
• Statistical Analysis Plan - Oct 30, 2020

More Information

Publications

None provided.

• Responsible Party: Alexion Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03459443
• Other Study ID Numbers: ACH471-205; 2017-002674-39
• First Posted: Mar 9, 2018
• Last Update Posted: Aug 11, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Alexion Pharmaceuticals: factor D; fD; alternative pathway; complement mediated disease; C3GN; DDD; idiopathic MPGN; MPGN Type I; MPGN Type II; MPGN Type III; Primary MPGN; MCGN; Mesangiocapillary Glomerulonephritis
• Additional relevant MeSH terms: Glomerulonephritis; Glomerulonephritis, Membranoproliferative

Study Results

Participant Flow

Pre-assignment Detail	To enroll in the study, participants were required to have a biopsy-confirmed diagnosis of C3 glomerulopathy (C3G) or immune-complex membranoproliferative glomerulonephritis (IC-MPGN).

Arm/Group Title	Danicopan
Arm/Group Description	Danicopan was to be administered to participants with C3G or IC-MPGN at a starting dose of 100 milligrams (mg) 3 times daily (TID) for the first 2 weeks, then the dosage was to be increased to 200 mg TID for the remainder of the study.
Period Title: Overall Study
STARTED	22
Received at Least 1 Dose of Study Drug	22
COMPLETED	0
NOT COMPLETED	22

Baseline Characteristics

Arm/Group Title	Danicopan
Arm/Group Description	Danicopan was to be administered to participants with C3G or IC-MPGN at a starting dose of 100 milligrams (mg) 3 times daily (TID) for the first 2 weeks, then the dosage was to be increased to 200 mg TID for the remainder of the study.
Overall Participants	22
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	24.3 (9.90)
Sex: Female, Male (Count of Participants)
Female	10 45.5%
Male	12 54.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	22 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 9.1%
Native Hawaiian or Other Pacific Islander	1 4.5%
Black or African American	0 0%
White	19 86.4%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline In Composite Biopsy Score At End Of Initial 12-Month Treatment Period
Description	The composite biopsy score was based on a score incorporating changes in the activity index, glomerular C3c staining, and glomerular macrophage infiltration at the end of the initial 12 months of treatment. The composite renal biopsy index scoring system ranged from 0 to 21, with higher scores indicating worse outcomes.
Time Frame	Baseline, end of initial 12-Month Treatment Period

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug and had analyzable data at the specified timepoints.

Arm/Group Title	Danicopan
Arm/Group Description	Danicopan was to be administered to participants with C3G or IC-MPGN at a starting dose of 100 milligrams (mg) 3 times daily (TID) for the first 2 weeks, then the dosage was to be increased to 200 mg TID for the remainder of the study.
Measure Participants	16
Baseline	10.6 (3.59)
End of 12-Month Initial Treatment Period	8.0 (4.53)
Change from Baseline	-0.9 (1.89)

2. Primary Outcome

Title	Participants With Reduction In Proteinuria At End Of Initial 12-Month Treatment Period
Description	Proteinuria reduction was defined as ≥30% decrease from baseline based on 24-hour urine protein (mg/day).
Time Frame	Baseline, end of initial 12-Month Treatment Period

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug and had analyzable data at the specified timepoints.

Arm/Group Title	Danicopan
Arm/Group Description	Danicopan was to be administered to participants with C3G or IC-MPGN at a starting dose of 100 milligrams (mg) 3 times daily (TID) for the first 2 weeks, then the dosage was to be increased to 200 mg TID for the remainder of the study.
Measure Participants	19
Number [participants]	8 36.4%

3. Secondary Outcome

Title	Change From Baseline In Proteinuria At End Of Initial 12-Month Treatment Period
Description	Proteinuria was assessed based on 24-hour urine collections at baseline and end of the initial 12-month Treatment Period.
Time Frame	Baseline, end of initial 12-Month Treatment Period

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug and had analyzable data at the specified timepoints.

Arm/Group Title	Danicopan
Arm/Group Description	Danicopan was to be administered to participants with C3G or IC-MPGN at a starting dose of 100 milligrams (mg) 3 times daily (TID) for the first 2 weeks, then the dosage was to be increased to 200 mg TID for the remainder of the study.
Measure Participants	22
Baseline	4252.28 (2684.959)
End of Initial 12-Month Treatment Period	3512.63 (3335.765)
Mean Change from Baseline	-671.11 (2695.592)

4. Secondary Outcome

Title	Percent Change From Baseline In Proteinuria At End Of Initial 12-Month Treatment Period
Description	Proteinuria was assessed based on 24-hour urine collections at baseline and end of initial 12-month Treatment Period.
Time Frame	Baseline, end of initial 12-Month Treatment Period

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug and had analyzable data at the specified timepoints.

Arm/Group Title	Danicopan
Arm/Group Description	Danicopan was to be administered to participants with C3G or IC-MPGN at a starting dose of 100 milligrams (mg) 3 times daily (TID) for the first 2 weeks, then the dosage was to be increased to 200 mg TID for the remainder of the study.
Measure Participants	19
Mean (Standard Deviation) [percent change]	-17.1 (53.17)

5. Secondary Outcome

Title	Slope Of Estimated Glomerular Filtration Rate (eGFR) From Baseline To End Of Initial 12-Month Treatment Period
Description	Slope of eGFR was estimated using a simple linear regression for each participant, including all data values from baseline until the end of the Initial 12-Month Treatment Period, with eGFR as the dependent variable and time as the independent variable.
Time Frame	End of initial 12-Month Treatment Period

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug and had analyzable data at the specified timepoints.

Arm/Group Title	Danicopan
Arm/Group Description	Danicopan was to be administered to participants with C3G or IC-MPGN at a starting dose of 100 milligrams (mg) 3 times daily (TID) for the first 2 weeks, then the dosage was to be increased to 200 mg TID for the remainder of the study.
Measure Participants	22
Mean (Standard Deviation) [mL/min/1.73 m^2 per month]	-1.24917 (1.811457)

6. Secondary Outcome

Title	Change From Baseline In eGFR At End Of Initial 12-Month Treatment Period
Description	Change from baseline in eGFR at end of initial 12-Month Treatment Period is presented.
Time Frame	Baseline, end of initial 12-Month Treatment Period

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug and had analyzable data at the specified timepoints.

Arm/Group Title	Danicopan
Arm/Group Description	Danicopan was to be administered to participants with C3G or IC-MPGN at a starting dose of 100 milligrams (mg) 3 times daily (TID) for the first 2 weeks, then the dosage was to be increased to 200 mg TID for the remainder of the study.
Measure Participants	22
Baseline	90.692 (35.4939)
End of Initial 12-Month Treatment Period	81.412 (38.3320)
Change from Baseline	-9.795 (14.3806)

7. Secondary Outcome

Title	Participants With Significant Improvement In eGFR Relative To Baseline At End Of Initial 12-Month Treatment Period
Description	Significant improvement relative to baseline was defined as a ≥ 25% increase from baseline in eGFR.
Time Frame	Baseline, end of initial 12-Month Treatment Period

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug and had analyzable data at the specified timepoints.

Arm/Group Title	Danicopan
Arm/Group Description	Danicopan was to be administered to participants with C3G or IC-MPGN at a starting dose of 100 milligrams (mg) 3 times daily (TID) for the first 2 weeks, then the dosage was to be increased to 200 mg TID for the remainder of the study.
Measure Participants	20
Number [participants]	0 0%

8. Secondary Outcome

Title	Change From Baseline in eGFR Over 12 Months of Treatment For Participants Meeting eGFR Inclusion Criteria
Description	Participants were eligible for enrollment if inclusion criteria were met including having an eGFR >=30 milliliters (mL)/minute (min)/1.73 square meter (m^2) at the time of screening or at any time over the preceding 4 weeks. This Outcome Measure was registered in case there were participants who were enrolled and ended up not meeting the Eligibility Criteria and was intended to report data for change from baseline in eGFR for only the participants who met the eligibility criteria (that is, participants who did not meet the eligibility criteria would have been excluded from analysis for this Outcome Measure). Since all enrolled participants met the Eligibility Criteria, none of the participants were excluded from this analysis. Therefore, this data is the same data that is presented in Outcome Measure #6 "Change From Baseline In eGFR At End Of Initial 12-Month Treatment Period". Change from baseline in eGFR at end of initial 12-Month Treatment Period is presented.
Time Frame	End of initial 12-Month Treatment Period

Outcome Measure Data

Analysis Population Description

All participants who received at least 1 dose of study drug and had analyzable data at the specified timepoints.

Arm/Group Title	Danicopan
Arm/Group Description	Danicopan was to be administered to participants with C3G or IC-MPGN at a starting dose of 100 milligrams (mg) 3 times daily (TID) for the first 2 weeks, then the dosage was to be increased to 200 mg TID for the remainder of the study.
Measure Participants	22
Baseline	90.692 (35.4939)
End of Initial 12-Month Treatment Period	81.412 (38.3320)
Change from Baseline	-9.795 (14.3806)

9. Secondary Outcome

Title	Change From Baseline In Measured GFR At The End Of The Initial 12-Month Treatment Period
Description	Data for this Outcome Measure was to be collected where available. None of the sites collected data for this Outcome Measure.
Time Frame	End of initial 12-Month Treatment Period

Outcome Measure Data

Analysis Population Description

Analysis was not performed, as data were not collected for this Outcome Measure.

Arm/Group Title	Danicopan
Arm/Group Description	Danicopan was to be administered to participants with C3G or IC-MPGN at a starting dose of 100 milligrams (mg) 3 times daily (TID) for the first 2 weeks, then the dosage was to be increased to 200 mg TID for the remainder of the study.
Measure Participants	0

Adverse Events

Time Frame	Day 1 (after dosing) up to 4 weeks after last dose of study drug (up to Week 108)
Arm/Group Title	Danicopan
Arm/Group Description	Danicopan was to be administered to participants with C3G or IC-MPGN at a starting dose of 100 milligrams (mg) 3 times daily (TID) for the first 2 weeks, then the dosage was to be increased to 200 mg TID for the remainder of the study.
All Cause Mortality
	Danicopan
	Affected / at Risk (%)	# Events
Total	0/22 (0%)
Serious Adverse Events
	Danicopan
	Affected / at Risk (%)	# Events
Total	3/22 (13.6%)
Cardiac disorders
Atrial fibrillation	1/22 (4.5%)	1
General disorders
Pyrexia	1/22 (4.5%)	1
Infections and infestations
Rhinovirus infection	1/22 (4.5%)	1
Renal and urinary disorders
Renal impairment	1/22 (4.5%)	1
Other (Not Including Serious) Adverse Events
	Danicopan
	Affected / at Risk (%)	# Events
Total	22/22 (100%)
Blood and lymphatic system disorders
Anaemia	5/22 (22.7%)	5
Leukopenia	2/22 (9.1%)	2
Thrombocytosis	2/22 (9.1%)	2
Anaemia macrocytic	1/22 (4.5%)	1
Leukocytosis	1/22 (4.5%)	1
Neutrophilia	1/22 (4.5%)	1
Cardiac disorders
Palpitations	2/22 (9.1%)	2
Left ventricular failure	1/22 (4.5%)	1
Ear and labyrinth disorders
Ear pain	2/22 (9.1%)	3
Vertigo	1/22 (4.5%)	1
Endocrine disorders
Hyperparathyroidism secondary	2/22 (9.1%)	2
Hypothyroidism	1/22 (4.5%)	1
Eye disorders
Periorbital oedema	2/22 (9.1%)	3
Conjunctivitis allergic	1/22 (4.5%)	1
Vision blurred	1/22 (4.5%)	1
Gastrointestinal disorders
Vomiting	6/22 (27.3%)	7
Diarrhoea	5/22 (22.7%)	7
Nausea	4/22 (18.2%)	4
Abdominal distension	2/22 (9.1%)	3
Abdominal pain upper	2/22 (9.1%)	2
Abdominal pain	1/22 (4.5%)	2
Constipation	1/22 (4.5%)	2
Abdominal pain lower	1/22 (4.5%)	1
Bowel movement irregularity	1/22 (4.5%)	1
Dry mouth	1/22 (4.5%)	1
Dyspepsia	1/22 (4.5%)	1
Gastrooesophageal reflux disease	1/22 (4.5%)	1
Haemorrhoids	1/22 (4.5%)	1
Hypertrophy of tongue papillae	1/22 (4.5%)	1
Paraesthesia oral	1/22 (4.5%)	1
Retroperitoneal haematoma	1/22 (4.5%)	1
General disorders
Pyrexia	11/22 (50%)	16
Oedema peripheral	8/22 (36.4%)	15
Fatigue	5/22 (22.7%)	7
Asthenia	4/22 (18.2%)	5
Influenza like illness	1/22 (4.5%)	2
Chills	1/22 (4.5%)	1
Facial pain	1/22 (4.5%)	1
Localised oedema	1/22 (4.5%)	1
Non-cardiac chest pain	1/22 (4.5%)	1
Oedema	1/22 (4.5%)	1
Pain	1/22 (4.5%)	1
Immune system disorders
Hypersensitivity	1/22 (4.5%)	1
Multiple allergies	1/22 (4.5%)	1
Infections and infestations
Gastroenteritis	6/22 (27.3%)	11
Pharyngitis	6/22 (27.3%)	6
Influenza	4/22 (18.2%)	4
Nasopharyngitis	3/22 (13.6%)	9
Upper respiratory tract infection	2/22 (9.1%)	4
Urinary tract infection	2/22 (9.1%)	4
Rhinitis	2/22 (9.1%)	2
Tonsillitis	1/22 (4.5%)	2
Viral infection	1/22 (4.5%)	2
Bacteriuria	1/22 (4.5%)	1
Conjunctivitis	1/22 (4.5%)	1
Corona virus infection	1/22 (4.5%)	1
Ear lobe infection	1/22 (4.5%)	1
Enterobiasis	1/22 (4.5%)	1
Herpes zoster	1/22 (4.5%)	1
Impetigo	1/22 (4.5%)	1
Respiratory tract infection viral	1/22 (4.5%)	1
Sinusitis	1/22 (4.5%)	1
Viral upper respiratory tract infection	3/22 (13.6%)	3
Bronchitis	2/22 (9.1%)	2
Injury, poisoning and procedural complications
Contusion	1/22 (4.5%)	1
Lip injury	1/22 (4.5%)	1
Post procedural haematuria	1/22 (4.5%)	1
Investigations
Blood creatine phosphokinase increased	5/22 (22.7%)	11
Blood creatinine increased	2/22 (9.1%)	3
Aspartate aminotransferase increased	2/22 (9.1%)	2
Alanine aminotransferase increased	1/22 (4.5%)	1
Blood potassium increased	1/22 (4.5%)	1
Blood uric acid increased	1/22 (4.5%)	1
Crystal urine present	1/22 (4.5%)	1
Electrocardiogram QT prolonged	1/22 (4.5%)	1
Haemoglobin decreased	1/22 (4.5%)	1
Lipids increased	1/22 (4.5%)	1
Transaminases increased	1/22 (4.5%)	1
Weight increased	1/22 (4.5%)	1
Blood potassium decreased	1/22 (4.5%)	1
Metabolism and nutrition disorders
Hyperkalaemia	5/22 (22.7%)	10
Hyperphosphataemia	2/22 (9.1%)	2
Metabolic acidosis	2/22 (9.1%)	2
Vitamin D deficiency	2/22 (9.1%)	2
Decreased appetite	1/22 (4.5%)	1
Dehydration	1/22 (4.5%)	1
Dyslipidaemia	1/22 (4.5%)	1
Hyperuricaemia	1/22 (4.5%)	1
Hypokalaemia	1/22 (4.5%)	1
Hypovitaminosis	1/22 (4.5%)	1
Iron deficiency	1/22 (4.5%)	1
Musculoskeletal and connective tissue disorders
Muscle spasms	3/22 (13.6%)	5
Back pain	3/22 (13.6%)	3
Pain in extremity	3/22 (13.6%)	3
Musculoskeletal chest pain	2/22 (9.1%)	3
Myalgia	2/22 (9.1%)	3
Arthralgia	1/22 (4.5%)	1
Bone pain	1/22 (4.5%)	1
Flank pain	1/22 (4.5%)	1
Joint effusion	1/22 (4.5%)	1
Muscle tightness	1/22 (4.5%)	1
Neck pain	1/22 (4.5%)	1
Pain in jaw	1/22 (4.5%)	1
Rhabdomyolysis	1/22 (4.5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin papilloma	1/22 (4.5%)	1
Nervous system disorders
Headache	6/22 (27.3%)	13
Dizziness	3/22 (13.6%)	3
Migraine	2/22 (9.1%)	2
Syncope	2/22 (9.1%)	2
Restless legs syndrome	1/22 (4.5%)	2
Dizziness postural	1/22 (4.5%)	1
Migraine with aura	1/22 (4.5%)	1
Somnolence	1/22 (4.5%)	1
Taste disorder	1/22 (4.5%)	1
Pregnancy, puerperium and perinatal conditions
Pregnancy	1/22 (4.5%)	1
Psychiatric disorders
Anxiety	2/22 (9.1%)	2
Abnormal dreams	1/22 (4.5%)	1
Renal and urinary disorders
Renal impairment	5/22 (22.7%)	6
Acute kidney injury	1/22 (4.5%)	1
Nephrotic syndrome	1/22 (4.5%)	1
Reproductive system and breast disorders
Menstruation irregular	2/22 (9.1%)	2
Oligomenorrhoea	1/22 (4.5%)	1
Premature menopause	1/22 (4.5%)	1
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	5/22 (22.7%)	8
Dyspnoea	4/22 (18.2%)	5
Cough	4/22 (18.2%)	4
Rhinorrhoea	3/22 (13.6%)	3
Productive cough	2/22 (9.1%)	2
Nasal congestion	1/22 (4.5%)	2
Dysphonia	1/22 (4.5%)	1
Upper-airway cough syndrome	1/22 (4.5%)	1
Wheezing	1/22 (4.5%)	1
Skin and subcutaneous tissue disorders
Rash	4/22 (18.2%)	4
Pruritus	2/22 (9.1%)	3
Erythema	2/22 (9.1%)	2
Acne	1/22 (4.5%)	1
Alopecia	1/22 (4.5%)	1
Dermatitis	1/22 (4.5%)	1
Dermatitis atopic	1/22 (4.5%)	1
Ingrowing nail	1/22 (4.5%)	1
Rash erythematous	1/22 (4.5%)	1
Skin lesion	1/22 (4.5%)	1
Surgical and medical procedures
Sinus operation	1/22 (4.5%)	1
Vascular disorders
Hypertension	2/22 (9.1%)	3
Hypertensive crisis	1/22 (4.5%)	3
Arteriovenous fistula	1/22 (4.5%)	1
Haematoma	1/22 (4.5%)	1
Hot flush	1/22 (4.5%)	1
Hypotension	1/22 (4.5%)	1
Pallor	1/22 (4.5%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.