Trial Outcomes & Findings for Safety Study of Soluble Ferric Pyrophosphate (SFP) in Dialysate in CKD Patients Receiving Chronic Hemodialysis (NCT NCT01503021)

NCT ID: NCT01503021

Last Updated: 2016-10-25

Results Overview

Adverse events for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 718 participants
• Primary outcome timeframe: Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study
• Results posted on: 2016-10-25

Participant Flow

Participant milestones

Measure	SFP/Placebo Soluble ferric pyrophosphate (SFP) 2 µmoles (110 µg) iron/L of dialysate in liquid bicarbonate concentrate x 2 weeks, then 1 week washout, then standard liquid bicarbonate concentrate without SFP x 2 weeks	Placebo/SFP Standard liquid bicarbonate concentrate without SFP x 2 weeks, then 1 week washout, then soluble ferric pyrophosphate (SFP) 2 µmoles (110 µg) iron/L of dialysate in liquid bicarbonate concentrate x 2 weeks.
Overall Study STARTED	360	358
Overall Study Dosed	351	352
Overall Study Completed Treatment	333	333
Overall Study COMPLETED	333	332
Overall Study NOT COMPLETED	27	26

Reasons for withdrawal

Measure	SFP/Placebo Soluble ferric pyrophosphate (SFP) 2 µmoles (110 µg) iron/L of dialysate in liquid bicarbonate concentrate x 2 weeks, then 1 week washout, then standard liquid bicarbonate concentrate without SFP x 2 weeks	Placebo/SFP Standard liquid bicarbonate concentrate without SFP x 2 weeks, then 1 week washout, then soluble ferric pyrophosphate (SFP) 2 µmoles (110 µg) iron/L of dialysate in liquid bicarbonate concentrate x 2 weeks.
Overall Study Adverse Event	7	6
Overall Study Death	0	2
Overall Study Lost to Follow-up	2	0
Overall Study Physician Decision	3	0
Overall Study Protocol Violation	1	3
Overall Study Withdrawal by Subject	9	8
Overall Study Moved, received transplant, etc.	5	7

Baseline Characteristics

Safety Study of Soluble Ferric Pyrophosphate (SFP) in Dialysate in CKD Patients Receiving Chronic Hemodialysis

Baseline characteristics by cohort

Measure	SFP/Placebo n=351 Participants Soluble ferric pyrophosphate (SFP) 2 µM (110 µg) iron/L of dialysate in liquid bicarbonate concentrate x 2 weeks, then 1 week washout, then standard liquid bicarbonate concentrate without SFP x 2 weeks	Placebo/SFP n=352 Participants Standard liquid bicarbonate concentrate without SFP x 2 weeks, then 1 week washout, then soluble ferric pyrophosphate (SFP) 2 µM (110 µg) iron/L of dialysate in liquid bicarbonate concentrate x 2 weeks.	Total n=703 Participants Total of all reporting groups
Age, Continuous	59.9 years STANDARD_DEVIATION 13.18 • n=93 Participants	59.5 years STANDARD_DEVIATION 13.30 • n=4 Participants	59.7 years STANDARD_DEVIATION 13.23 • n=27 Participants
Sex: Female, Male Female	137 Participants n=93 Participants	141 Participants n=4 Participants	278 Participants n=27 Participants
Sex: Female, Male Male	214 Participants n=93 Participants	211 Participants n=4 Participants	425 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	90 Participants n=93 Participants	106 Participants n=4 Participants	196 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	261 Participants n=93 Participants	246 Participants n=4 Participants	507 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	5 Participants n=93 Participants	0 Participants n=4 Participants	5 Participants n=27 Participants
Race (NIH/OMB) Asian	6 Participants n=93 Participants	8 Participants n=4 Participants	14 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	154 Participants n=93 Participants	145 Participants n=4 Participants	299 Participants n=27 Participants
Race (NIH/OMB) White	185 Participants n=93 Participants	194 Participants n=4 Participants	379 Participants n=27 Participants
Race (NIH/OMB) More than one race	1 Participants n=93 Participants	5 Participants n=4 Participants	6 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants

PRIMARY outcome

Timeframe: Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study

Population: All participants who received at least one dose of study drug (SFP or placebo, as applicable).

Adverse events for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention.

Outcome measures

Measure	Soluble Ferric Pyrophosphate n=693 Participants Parent Study: Blinded soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.	Placebo n=687 Participants Parent Study: Blinded standard liquid bicarbonate concentrate	Open-label Soluble Ferric Pyrophosphate n=309 Participants Extension Study: Open-label soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.
Incidence of Treatment-emergent Adverse Events	31.6 percentage of participants	35.1 percentage of participants	95.1 percentage of participants

PRIMARY outcome

Timeframe: Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study

Population: All participants who received at least one dose of study drug (SFP or placebo, as applicable).

Adverse events for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. For each adverse event, investigators assessed whether the event met the protocol criteria for intradialytic hypotension. Intradialytic hypotension events were only to have been reported as adverse events if they exceeded the individual subject's baseline pattern of intradialytic hypotension.

Outcome measures

Measure	Soluble Ferric Pyrophosphate n=693 Participants Parent Study: Blinded soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.	Placebo n=687 Participants Parent Study: Blinded standard liquid bicarbonate concentrate	Open-label Soluble Ferric Pyrophosphate n=309 Participants Extension Study: Open-label soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.
Incidence of Treatment-emergent Adverse Events of Intradialytic Hypotension	4.3 percentage of participants	4.9 percentage of participants	12.6 percentage of participants

PRIMARY outcome

Timeframe: Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study

Population: All participants who received at least one dose of study drug (SFP or placebo, as applicable).

Adverse events for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. For each adverse event, investigators assessed whether the event met protocol criteria for suspected hypersensitivity reactions.

Outcome measures

Measure	Soluble Ferric Pyrophosphate n=693 Participants Parent Study: Blinded soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.	Placebo n=687 Participants Parent Study: Blinded standard liquid bicarbonate concentrate	Open-label Soluble Ferric Pyrophosphate n=309 Participants Extension Study: Open-label soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.
Incidence of Related Suspected Hypersensitivity Reactions	0 percentage of participants	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study

Population: All participants who received at least one dose of study drug (SFP or placebo, as applicable).

Adverse events for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Adverse event terms meeting criteria for composite cardiovascular events were pre-specified in the statistical analysis plan for the study.

Outcome measures

Measure	Soluble Ferric Pyrophosphate n=693 Participants Parent Study: Blinded soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.	Placebo n=687 Participants Parent Study: Blinded standard liquid bicarbonate concentrate	Open-label Soluble Ferric Pyrophosphate n=309 Participants Extension Study: Open-label soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.
Incidence of Composite Cardiovascular Events	1.0 percentage of participants	0.7 percentage of participants	13.6 percentage of participants

SECONDARY outcome

Timeframe: Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study

Population: All participants who received at least one dose of study drug (SFP or placebo, as applicable).

Adverse events for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Adverse event terms meeting criteria for hemodialysis vascular access thrombotic events were pre-specified in the statistical analysis plan for the study.

Outcome measures

Measure	Soluble Ferric Pyrophosphate n=693 Participants Parent Study: Blinded soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.	Placebo n=687 Participants Parent Study: Blinded standard liquid bicarbonate concentrate	Open-label Soluble Ferric Pyrophosphate n=309 Participants Extension Study: Open-label soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.
Incidence of Hemodialysis Vascular Access Thrombotic Events	0.6 percentage of participants	0.6 percentage of participants	17.8 percentage of participants

SECONDARY outcome

Timeframe: Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study

Population: All participants who received at least one dose of study drug (SFP or placebo, as applicable).

Adverse events for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Adverse event terms meeting criteria for other thrombotic events were pre-specified in the statistical analysis plan for the study.

Outcome measures

Measure	Soluble Ferric Pyrophosphate n=693 Participants Parent Study: Blinded soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.	Placebo n=687 Participants Parent Study: Blinded standard liquid bicarbonate concentrate	Open-label Soluble Ferric Pyrophosphate n=309 Participants Extension Study: Open-label soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.
Incidence of Other Thrombotic Events	0 percentage of participants	0.1 percentage of participants	1.9 percentage of participants

SECONDARY outcome

Timeframe: Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study

Population: All participants who received at least one dose of study drug (SFP or placebo, as applicable).

Adverse events for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Adverse events of systemic/serious infections were defined in the statistical analysis plan for the study to include infections for which the subject was administered at least 3 doses of an IV antibiotic, and infections for which the subject was hospitalized.

Outcome measures

Measure	Soluble Ferric Pyrophosphate n=693 Participants Parent Study: Blinded soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.	Placebo n=687 Participants Parent Study: Blinded standard liquid bicarbonate concentrate	Open-label Soluble Ferric Pyrophosphate n=309 Participants Extension Study: Open-label soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.
Incidence of Systemic/Serious Infections	0.4 percentage of participants	0.9 percentage of participants	11.3 percentage of participants

SECONDARY outcome

Timeframe: Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study

Population: All participants who received at least one dose of study drug (SFP or placebo, as applicable).

Adverse events for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. For each adverse event, investigators assessed whether the event met seriousness criteria.

Outcome measures

Measure	Soluble Ferric Pyrophosphate n=693 Participants Parent Study: Blinded soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.	Placebo n=687 Participants Parent Study: Blinded standard liquid bicarbonate concentrate	Open-label Soluble Ferric Pyrophosphate n=309 Participants Extension Study: Open-label soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.
Incidence of Serious Adverse Events	4.3 percentage of participants	5.1 percentage of participants	46.6 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-dialysis and post-dialysis during study week 2 of the Parent (Crossover) Study

Population: All participants who received at least one dose of study drug (SFP or placebo, as applicable).

Serum iron was assessed from samples obtained pre-dialysis and post-dialysis at a single hemodialysis during study week 2. Because of the crossover nature of the study, the week 2 values reflect effects of SFP in the SFP/Placebo arm and effects of Placebo in the Placebo/SFP arm.

Outcome measures

Measure	Soluble Ferric Pyrophosphate n=307 Participants Parent Study: Blinded soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.	Placebo n=311 Participants Parent Study: Blinded standard liquid bicarbonate concentrate	Open-label Soluble Ferric Pyrophosphate Extension Study: Open-label soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.
Serum Iron Change From Pre-dialysis to Post-dialysis at Week 2 Pre-dialysis	13.66 micromoles per liter Standard Deviation 5.435	13.65 micromoles per liter Standard Deviation 5.299	—
Serum Iron Change From Pre-dialysis to Post-dialysis at Week 2 Post-dialysis	38.60 micromoles per liter Standard Deviation 10.151	14.97 micromoles per liter Standard Deviation 7.753	—
Serum Iron Change From Pre-dialysis to Post-dialysis at Week 2 Change from pre-dialysis to post-dialysis	24.91 micromoles per liter Standard Deviation 9.243	1.36 micromoles per liter Standard Deviation 5.447	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-dialysis and post-dialysis during study week 5 of the Parent (Crossover) Study

Population: All participants who received at least one dose of study drug (SFP or placebo, as applicable).

Serum iron was assessed from samples obtained pre-dialysis and post-dialysis at a single hemodialysis during study week 5. Because of the crossover nature of the study, the week 5 values reflect effects of Placebo in the SFP/Placebo arm and effects of SFP in the Placebo/SFP arm.

Outcome measures

Measure	Soluble Ferric Pyrophosphate n=299 Participants Parent Study: Blinded soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.	Placebo n=303 Participants Parent Study: Blinded standard liquid bicarbonate concentrate	Open-label Soluble Ferric Pyrophosphate Extension Study: Open-label soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.
Serum Iron Change From Pre-dialysis to Post-dialysis at Week 5 Pre-dialysis	12.97 micromoles per liter Standard Deviation 4.731	13.02 micromoles per liter Standard Deviation 4.856	—
Serum Iron Change From Pre-dialysis to Post-dialysis at Week 5 Post-dialysis	13.98 micromoles per liter Standard Deviation 7.884	37.79 micromoles per liter Standard Deviation 11.183	—
Serum Iron Change From Pre-dialysis to Post-dialysis at Week 5 Change from pre-dialysis to post-dialysis	1.12 micromoles per liter Standard Deviation 6.834	24.82 micromoles per liter Standard Deviation 9.827	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-dialysis and post-dialysis during study week 2 of the Parent (Crossover) Study

Population: All participants who received at least one dose of study drug (SFP or placebo, as applicable).

Unsaturated iron-binding capacity was assessed from samples obtained pre-dialysis and post-dialysis at a single hemodialysis during study week 2. Because of the crossover nature of the study, the week 2 values reflect effects of SFP in the SFP/Placebo arm and effects of Placebo in the Placebo/SFP arm.

Outcome measures

Measure	Soluble Ferric Pyrophosphate n=351 Participants Parent Study: Blinded soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.	Placebo n=352 Participants Parent Study: Blinded standard liquid bicarbonate concentrate	Open-label Soluble Ferric Pyrophosphate Extension Study: Open-label soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.
Unsaturated Iron-binding Capacity Change From Pre-dialysis to Post-dialysis at Week 2 Pre-dialysis	27.95 micromoles per liter Standard Deviation 6.310	28.05 micromoles per liter Standard Deviation 7.442	—
Unsaturated Iron-binding Capacity Change From Pre-dialysis to Post-dialysis at Week 2 Post-dialysis	11.44 micromoles per liter Standard Deviation 6.899	30.49 micromoles per liter Standard Deviation 8.909	—
Unsaturated Iron-binding Capacity Change From Pre-dialysis to Post-dialysis at Week 2 Change from pre-dialysis to post-dialysis	-16.47 micromoles per liter Standard Deviation 7.040	2.49 micromoles per liter Standard Deviation 4.910	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-dialysis and post-dialysis during study week 5 of the Parent (Crossover) Study

Population: All participants who received at least one dose of study drug (SFP or placebo, as applicable).

Unsaturated iron-binding capacity was assessed from samples obtained pre-dialysis and post-dialysis at a single hemodialysis during study week 5. Because of the crossover nature of the study, the week 5 values reflect effects of Placebo in the SFP/Placebo arm and effects of SFP in the Placebo/SFP arm.

Outcome measures

Measure	Soluble Ferric Pyrophosphate n=351 Participants Parent Study: Blinded soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.	Placebo n=352 Participants Parent Study: Blinded standard liquid bicarbonate concentrate	Open-label Soluble Ferric Pyrophosphate Extension Study: Open-label soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.
Unsaturated Iron-binding Capacity Change From Pre-dialysis to Post-dialysis at Week 5 Pre-dialysis	28.80 micromoles per liter Standard Deviation 6.745	29.05 micromoles per liter Standard Deviation 7.311	—
Unsaturated Iron-binding Capacity Change From Pre-dialysis to Post-dialysis at Week 5 Post-dialysis	30.95 micromoles per liter Standard Deviation 8.488	12.41 micromoles per liter Standard Deviation 8.463	—
Unsaturated Iron-binding Capacity Change From Pre-dialysis to Post-dialysis at Week 5 Change from pre-dialysis to post-dialysis	2.05 micromoles per liter Standard Deviation 5.333	-16.68 micromoles per liter Standard Deviation 7.452	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-dialysis and post-dialysis during study week 2 of the Parent (Crossover) Study

Population: All participants who received at least one dose of study drug (SFP or placebo, as applicable).

Transferrin saturation (based on TIBC derived from transferrin levels) was assessed from samples obtained pre-dialysis and post-dialysis at a single hemodialysis during study week 2. Because of the crossover nature of the study, the week 2 values reflect effects of SFP in the SFP/Placebo arm and effects of Placebo in the Placebo/SFP arm.

Outcome measures

Measure	Soluble Ferric Pyrophosphate n=351 Participants Parent Study: Blinded soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.	Placebo n=352 Participants Parent Study: Blinded standard liquid bicarbonate concentrate	Open-label Soluble Ferric Pyrophosphate Extension Study: Open-label soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.
Transferrin Saturation Change From Pre-dialysis to Post-dialysis at Week 2 Pre-dialysis	30.31 percent transferrin saturation Standard Deviation 11.357	30.46 percent transferrin saturation Standard Deviation 11.849	—
Transferrin Saturation Change From Pre-dialysis to Post-dialysis at Week 2 Post-dialysis	80.85 percent transferrin saturation Standard Deviation 17.646	30.23 percent transferrin saturation Standard Deviation 14.397	—
Transferrin Saturation Change From Pre-dialysis to Post-dialysis at Week 2 Change from pre-dialysis to post-dialysis	50.44 percent transferrin saturation Standard Deviation 17.442	-0.25 percent transferrin saturation Standard Deviation 10.348	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Pre-dialysis and post-dialysis during study week 5 of the Parent (Crossover) Study

Population: All participants who received at least one dose of study drug (SFP or placebo, as applicable).

Transferrin saturation (based on TIBC derived from transferrin levels) was assessed from samples obtained pre-dialysis and post-dialysis at a single hemodialysis during study week 5. Because of the crossover nature of the study, the week 5 values reflect effects of Placebo in the SFP/Placebo arm and effects of SFP in the Placebo/SFP arm.

Outcome measures

Measure	Soluble Ferric Pyrophosphate n=351 Participants Parent Study: Blinded soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.	Placebo n=352 Participants Parent Study: Blinded standard liquid bicarbonate concentrate	Open-label Soluble Ferric Pyrophosphate Extension Study: Open-label soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.
Transferrin Saturation Change From Pre-dialysis to Post-dialysis at Week 5 Pre-dialysis	26.75 percent transferrin saturation Standard Deviation 10.302	28.88 percent transferrin saturation Standard Deviation 10.585	—
Transferrin Saturation Change From Pre-dialysis to Post-dialysis at Week 5 Post-dialysis	28.73 percent transferrin saturation Standard Deviation 15.818	79.18 percent transferrin saturation Standard Deviation 20.008	—
Transferrin Saturation Change From Pre-dialysis to Post-dialysis at Week 5 Change from pre-dialysis to post-dialysis	0.10 percent transferrin saturation Standard Deviation 13.792	50.42 percent transferrin saturation Standard Deviation 18.163	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, up to 53 weeks for Extension Study

Population: All participants who received at least one dose of study drug (SFP or placebo, as applicable).

The baseline and end of treatment predialysis ferritin levels were evaluated for the 52-week extension study to determine whether soluble ferric pyrophosphate increases iron stores.

Outcome measures

Measure	Soluble Ferric Pyrophosphate n=309 Participants Parent Study: Blinded soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.	Placebo Parent Study: Blinded standard liquid bicarbonate concentrate	Open-label Soluble Ferric Pyrophosphate Extension Study: Open-label soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.
Ferritin Baseline	653.0 micrograms per liter Standard Deviation 288.70	—	—
Ferritin End of Treatment	520.3 micrograms per liter Standard Deviation 341.84	—	—
Ferritin Change from Baseline	-132.0 micrograms per liter Standard Deviation 311.15	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, up to 53 weeks for Extension Study

Population: All participants who received at least one dose of study drug (SFP or placebo, as applicable).

The baseline and end of treatment predialysis serum iron levels were evaluated for the 52-week extension study to determine the effect of soluble ferric pyrophosphate on serum iron.

Outcome measures

Measure	Soluble Ferric Pyrophosphate n=309 Participants Parent Study: Blinded soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.	Placebo Parent Study: Blinded standard liquid bicarbonate concentrate	Open-label Soluble Ferric Pyrophosphate Extension Study: Open-label soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.
Serum Iron Baseline	12.650 micromoles per liter Standard Deviation 4.6488	—	—
Serum Iron End of Treatment	11.815 micromoles per liter Standard Deviation 5.3443	—	—
Serum Iron Change from Baseline	-0.772 micromoles per liter Standard Deviation 5.2686	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, up to 53 weeks for Extension Study

Population: All participants who received at least one dose of study drug (SFP or placebo, as applicable).

The baseline and end of treatment predialysis transferrin saturation were evaluated for the 52-week extension study to confirm clearance of iron derived from soluble ferric pyrophosphate.

Outcome measures

Measure	Soluble Ferric Pyrophosphate n=309 Participants Parent Study: Blinded soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.	Placebo Parent Study: Blinded standard liquid bicarbonate concentrate	Open-label Soluble Ferric Pyrophosphate Extension Study: Open-label soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.
Transferrin Saturation Baseline	30.050 percent transferrin saturation Standard Deviation 10.0504	—	—
Transferrin Saturation End of Treatment	28.114 percent transferrin saturation Standard Deviation 11.5075	—	—
Transferrin Saturation Change from Baseline	-1.835 percent transferrin saturation Standard Deviation 11.7221	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study

Population: All participants who received at least one dose of study drug (SFP or placebo, as applicable).

The peak alanine aminotransferase and the peak total bilirubin levels were evaluated per patient. Laboratory values for a given intervention (SFP or Placebo) are counted from the date of the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Patients with alanine aminotransferase more than three times the upper limit of normal and also total bilirubin more than two times the upper limit of normal are counted.

Outcome measures

Measure	Soluble Ferric Pyrophosphate n=693 Participants Parent Study: Blinded soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.	Placebo n=687 Participants Parent Study: Blinded standard liquid bicarbonate concentrate	Open-label Soluble Ferric Pyrophosphate n=309 Participants Extension Study: Open-label soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.
Incidence of Patients Meeting Hy's Law Criteria	0 participants	0 participants	0 participants

Adverse Events

Soluble Ferric Pyrophosphate

Serious events: 30 serious events

Other events: 123 other events

Deaths: 0 deaths

Placebo

Serious events: 35 serious events

Other events: 131 other events

Deaths: 0 deaths

Open-label Soluble Ferric Pyrophosphate

Serious events: 144 serious events

Other events: 253 other events

Deaths: 0 deaths

Serious adverse events

Measure	Soluble Ferric Pyrophosphate n=693 participants at risk Parent Study: Blinded soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.	Placebo n=687 participants at risk Parent Study: Blinded standard liquid bicarbonate concentrate	Open-label Soluble Ferric Pyrophosphate n=309 participants at risk Extension Study: Open-label soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.
Blood and lymphatic system disorders Anaemia	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	1.6% 5/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Cardiac disorders Acute myocardial infarction	0.58% 4/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	1.6% 5/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Cardiac disorders Angina pectoris	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	1.6% 5/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Cardiac disorders Atrial fibrillation	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	1.3% 4/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Cardiac disorders Cardiac arrest	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	1.3% 4/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Cardiac disorders Cardiac failure congestive	0.14% 1/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.29% 2/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	1.9% 6/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Cardiac disorders Coronary artery disease	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.29% 2/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	1.6% 5/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Cardiac disorders Myocardial infarction	0.14% 1/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.44% 3/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Cardiac disorders Pericardial effusion	0.14% 1/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.65% 2/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Cardiac disorders Sinus tachycardia	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Gastrointestinal disorders Anal fistula	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Gastrointestinal disorders Duodenal ulcer haemorrhage	0.14% 1/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Gastrointestinal disorders Dysphagia	0.14% 1/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Gastrointestinal disorders Enterovesical fistula	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Gastrointestinal disorders Impaired gastric emptying	0.14% 1/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Gastrointestinal disorders Pancreatitis	0.14% 1/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.65% 2/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
General disorders Gait disturbance	0.14% 1/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
General disorders Systemic inflammatory response syndrome	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Hepatobiliary disorders Cholecystitis acute	0.14% 1/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Bacteraemia	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	1.3% 4/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Bronchitis	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.29% 2/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	1.9% 6/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Cholecystitis infective	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Device related infection	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Gastroenteritis	0.14% 1/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.65% 2/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Lobar pneumonia	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Pneumonia	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.73% 5/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	2.3% 7/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Pneumonia primary atypical	0.14% 1/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Streptococcal sepsis	0.14% 1/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Viral infection	0.14% 1/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Injury, poisoning and procedural complications Arteriovenous fistula site haemorrhage	0.14% 1/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Injury, poisoning and procedural complications Arteriovenous fistula thrombosis	0.14% 1/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	1.6% 5/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Injury, poisoning and procedural complications Hip fracture	0.14% 1/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.29% 2/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.65% 2/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Injury, poisoning and procedural complications Postoperative ileus	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Injury, poisoning and procedural complications Procedural hypotension	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Injury, poisoning and procedural complications Vascular graft thrombosis	0.14% 1/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	2.3% 7/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Metabolism and nutrition disorders Hyperkalaemia	0.29% 2/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	2.3% 7/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Metabolism and nutrition disorders Hypoglycaemia	0.29% 2/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.97% 3/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Nervous system disorders Cerebrovascular accident	0.14% 1/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Nervous system disorders Convulsion	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Nervous system disorders Metabolic encephalopathy	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.97% 3/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Nervous system disorders Syncope	0.29% 2/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	1.6% 5/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Nervous system disorders Transient ischaemic attack	0.14% 1/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.97% 3/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Psychiatric disorders Bipolar disorder	0.14% 1/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.14% 1/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.29% 2/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.97% 3/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.14% 1/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.97% 3/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.14% 1/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.65% 2/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.97% 3/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	1.3% 4/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Respiratory, thoracic and mediastinal disorders Respiratory arrest	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Vascular disorders Deep vein thrombosis	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Vascular disorders Hypertensive crisis	0.14% 1/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.65% 2/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Vascular disorders Peripheral vascular disorder	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	1.3% 4/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Blood and lymphatic system disorders Coagulopathy	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Blood and lymphatic system disorders Haemorrhagic anaemia	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Cardiac disorders Angina unstable	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.97% 3/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Cardiac disorders Arteriosclerosis coronary artery	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.65% 2/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Cardiac disorders Ischaemic cardiomyopathy	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Cardiac disorders Sick sinus syndrome	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Cardiac disorders Tachycardia	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Cardiac disorders Ventricular tachycardia	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	2.6% 8/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Gastrointestinal disorders Abdominal pain	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.65% 2/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.65% 2/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Gastrointestinal disorders Abdominal pain lower	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Gastrointestinal disorders Colitis	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Gastrointestinal disorders Duodenitis	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Gastrointestinal disorders Gastric ulcer	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Gastrointestinal disorders Intestinal perforation	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Gastrointestinal disorders Oesophagitis	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
General disorders Non-cardiac chest pain	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	1.3% 4/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
General disorders Asthenia	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.65% 2/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
General disorders Chest pain	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.65% 2/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
General disorders Medical device complication	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.65% 2/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
General disorders Pyrexia	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.65% 2/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
General disorders Adverse drug reaction	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
General disorders Device pacing issue	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
General disorders Malaise	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
General disorders Sudden death	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Hepatobiliary disorders Cholelithiasis	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.97% 3/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Hepatobiliary disorders Biliary dyskinesia	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.65% 2/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Hepatobiliary disorders Cholecystitis	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.65% 2/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Hepatobiliary disorders Bile duct obstruction	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Hepatobiliary disorders Biliary colic	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Hepatobiliary disorders Hepatic necrosis	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Sepsis	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	1.9% 6/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Cellulitis	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	1.6% 5/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Gangrene	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	1.3% 4/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Septic shock	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	1.3% 4/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Diabetic foot infection	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.97% 3/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Urinary tract infection	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.97% 3/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Arteriovenous fistula site infection	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.65% 2/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Staphylococcal bacteraemia	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.65% 2/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Abscess limb	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Arteriovenous graft site infection	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Chest wall abscess	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Clostridium difficile colitis	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Escherichia urinary tract infection	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Gastroenteritis viral	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Nasal abscess	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Necrotising fasciitis	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Osteomyelitis	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Pharyngitis	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Pneumonia influenzal	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Streptococcal bacteraemia	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Wound sepsis	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Injury, poisoning and procedural complications Areriovenous fistula aneurysm	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.65% 2/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Injury, poisoning and procedural complications Arteriovenous fistula site complication	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.65% 2/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Injury, poisoning and procedural complications Arteriovenous graft site haemorrhage	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Injury, poisoning and procedural complications Burns third degree	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Injury, poisoning and procedural complications Contusion	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Injury, poisoning and procedural complications Fall	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Injury, poisoning and procedural complications Muscle strain	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Injury, poisoning and procedural complications Post procedural myocardial infarction	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Injury, poisoning and procedural complications Toxicity to various agents	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Injury, poisoning and procedural complications Vascular graft complication	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Injury, poisoning and procedural complications Wrist fracture	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Metabolism and nutrition disorders Fluid overload	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	2.9% 9/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Metabolism and nutrition disorders Diabetic foot	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Metabolism and nutrition disorders Failure to thrive	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Nervous system disorders Hepatic encephalopathy	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.97% 3/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Nervous system disorders Uraemic encephalopathy	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.65% 2/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Nervous system disorders Haemorrhage intracranial	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Nervous system disorders Subarachnoid haemorrhage	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Nervous system disorders Vascular dementia	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Psychiatric disorders Mental status changes	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.65% 2/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Respiratory, thoracic and mediastinal disorders Mediastinal haemorrhage	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Respiratory, thoracic and mediastinal disorders Pleurisy	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Vascular disorders Peripheral arterial occlusive disease	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.65% 2/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Vascular disorders Haematoma	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Vascular disorders Hypertension	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Vascular disorders Hypotension	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Vascular disorders Peripheral embolism	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Vascular disorders Peripheral ischaemia	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Vascular disorders Steal syndrome	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Vascular disorders Subclavian vein thrombosis	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Vascular disorders Superior vena cava syndrome	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Vascular disorders Venous occlusion	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Musculoskeletal and connective tissue disorders Bone cyst	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Musculoskeletal and connective tissue disorders Plantar fasciitis	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Musculoskeletal and connective tissue disorders Systemic lupus erythematosus	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer in situ	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastatic renal cell carcinoma	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Immune system disorders Anaphylactic reaction	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Immune system disorders Drug hypersensitivity	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Renal and urinary disorders Azotaemia	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Renal and urinary disorders Nephrolithiasis	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Skin and subcutaneous tissue disorders Rash macular	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Congenital, familial and genetic disorders Gastrointestinal arteriovenous malformation	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Eye disorders Retinal artery embolism	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Investigations International normalised ratio increased	0.00% 0/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.32% 1/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.

Other adverse events

Measure	Soluble Ferric Pyrophosphate n=693 participants at risk Parent Study: Blinded soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.	Placebo n=687 participants at risk Parent Study: Blinded standard liquid bicarbonate concentrate	Open-label Soluble Ferric Pyrophosphate n=309 participants at risk Extension Study: Open-label soluble ferric pyrophosphate administered via the liquid bicarbonate concentrate to yield a final dialysate concentration of 2 micromolar (110 micrograms) iron/liter.
Blood and lymphatic system disorders Anaemia	1.2% 8/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.87% 6/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	6.5% 20/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Gastrointestinal disorders Diarrhoea	1.3% 9/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	2.2% 15/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	17.2% 53/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Gastrointestinal disorders Nausea	1.7% 12/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	1.7% 12/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	19.7% 61/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Gastrointestinal disorders Vomiting	1.2% 8/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	1.2% 8/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	12.0% 37/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
General disorders Oedema peripheral	0.72% 5/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	1.2% 8/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	11.7% 36/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Upper respiratory tract infection	0.58% 4/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	1.3% 9/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	8.4% 26/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Injury, poisoning and procedural complications Arteriovenous fistula site complication	1.6% 11/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	1.3% 9/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	18.1% 56/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Injury, poisoning and procedural complications Procedural hypotension	4.6% 32/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	4.7% 32/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	12.6% 39/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Musculoskeletal and connective tissue disorders Muscle spasms	2.5% 17/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	2.2% 15/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	6.5% 20/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Nervous system disorders Dizziness	0.72% 5/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	1.0% 7/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	12.0% 37/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Gastrointestinal disorders Abdominal pain	0.43% 3/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.00% 0/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	7.8% 24/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Respiratory, thoracic and mediastinal disorders Cough	0.58% 4/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	1.5% 10/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	8.1% 25/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.2% 8/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.29% 2/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	8.7% 27/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Vascular disorders Hypertension	1.0% 7/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.73% 5/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	8.4% 26/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Injury, poisoning and procedural complications Arteriovenous fistula thrombosis	0.43% 3/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.44% 3/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	7.8% 24/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Musculoskeletal and connective tissue disorders Back pain	0.43% 3/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	10.4% 32/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Metabolism and nutrition disorders Fluid overload	0.72% 5/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	5.8% 18/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Injury, poisoning and procedural complications Haemodialysis-induced symptom	0.58% 4/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.44% 3/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	15.9% 49/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Metabolism and nutrition disorders Hyperkalaemia	0.14% 1/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.58% 4/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	6.5% 20/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Nasopharyngitis	0.58% 4/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	5.2% 16/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Musculoskeletal and connective tissue disorders Pain in extremity	0.29% 2/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.58% 4/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	10.4% 32/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
General disorders Pyrexia	0.14% 1/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.15% 1/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	8.7% 27/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Infections and infestations Urinary tract infection	0.29% 2/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.44% 3/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	6.8% 21/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Injury, poisoning and procedural complications Vascular graft complication	0.29% 2/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.29% 2/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	8.7% 27/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.
Injury, poisoning and procedural complications Vascular graft thrombosis	0.29% 2/693 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	0.44% 3/687 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.	7.4% 23/309 • Up to 7 weeks for the Parent (Crossover) Study and up to 53 weeks for Extension Study Adverse events for a given intervention are counted from the first day of dosing of the intervention until 7 days after the last day of dosing of the intervention. Information regarding adverse events was elicited from participants using non-leading questions at each study visit, which generally occurred 3 times per week during the study.

Additional Information

Senior Director, Clinical Research

Rockwell Medical, Inc

Phone: 248-960-9009

Email: rd@rockwellmed.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60