Trial Outcomes & Findings for A Two-Part, Single-Blind, Phase 3 Study Evaluating the Efficacy and Safety of Patiromer for the Treatment of Hyperkalemia (OPAL) (NCT NCT01810939)
NCT ID: NCT01810939
Last Updated: 2021-06-03
Results Overview
The primary analysis endpoint is the change from Baseline at Week 4. The estimate of the change at Week 4 is from a repeated measures model, which includes data from Weeks 1, 2, 3 and 4. The analysis includes all intent to treat participants who had a serum potassium result at baseline and at least one weekly post-baseline visit (i.e. Part A Week 1 or later) and excludes six participants who had no result collected after Day 3).
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
243 participants
Primary outcome timeframe
Part A Baseline to Part A Week 4
Results posted on
2021-06-03
Participant Flow
Participant milestones
| Measure |
Part A Patiromer
Participants were administered patiromer starting dose of 8.4 g or 16.8 g daily as a divided dose twice a day, orally, for 4 weeks.
|
Part B Patiromer
Participants continued on the same daily patiromer dose as administered at the time of the Part A Week 4 Visit for 8 weeks.
|
Part B Placebo
Participants were administered placebo orally twice a day for 8 weeks.
|
|---|---|---|---|
|
Part A Treatment Period
STARTED
|
243
|
0
|
0
|
|
Part A Treatment Period
COMPLETED
|
219
|
0
|
0
|
|
Part A Treatment Period
NOT COMPLETED
|
24
|
0
|
0
|
|
Part B Placebo-Controlled Withdrawal
STARTED
|
0
|
55
|
52
|
|
Part B Placebo-Controlled Withdrawal
COMPLETED
|
0
|
45
|
30
|
|
Part B Placebo-Controlled Withdrawal
NOT COMPLETED
|
0
|
10
|
22
|
Reasons for withdrawal
| Measure |
Part A Patiromer
Participants were administered patiromer starting dose of 8.4 g or 16.8 g daily as a divided dose twice a day, orally, for 4 weeks.
|
Part B Patiromer
Participants continued on the same daily patiromer dose as administered at the time of the Part A Week 4 Visit for 8 weeks.
|
Part B Placebo
Participants were administered placebo orally twice a day for 8 weeks.
|
|---|---|---|---|
|
Part A Treatment Period
Non-compliance with Study Drug
|
1
|
0
|
0
|
|
Part A Treatment Period
Protocol Violation
|
2
|
0
|
0
|
|
Part A Treatment Period
Adverse Event
|
10
|
0
|
0
|
|
Part A Treatment Period
Withdrawal by Subject
|
5
|
0
|
0
|
|
Part A Treatment Period
Protocol-specified (eGFR)
|
2
|
0
|
0
|
|
Part A Treatment Period
Protocol-specified (High K+)
|
3
|
0
|
0
|
|
Part A Treatment Period
Protocol-specified (Low K+)
|
1
|
0
|
0
|
|
Part B Placebo-Controlled Withdrawal
Physician Decision
|
0
|
1
|
1
|
|
Part B Placebo-Controlled Withdrawal
Non-compliance with Study Drug
|
0
|
1
|
0
|
|
Part B Placebo-Controlled Withdrawal
Adverse Event
|
0
|
1
|
1
|
|
Part B Placebo-Controlled Withdrawal
Death
|
0
|
0
|
1
|
|
Part B Placebo-Controlled Withdrawal
Withdrawal by Subject
|
0
|
0
|
1
|
|
Part B Placebo-Controlled Withdrawal
Protocol-specified (eGFR)
|
0
|
1
|
1
|
|
Part B Placebo-Controlled Withdrawal
Protocol-specified (K+ result)
|
0
|
1
|
2
|
|
Part B Placebo-Controlled Withdrawal
Protocol-specified (High K+)
|
0
|
2
|
14
|
|
Part B Placebo-Controlled Withdrawal
Protocol-specified (Low K+)
|
0
|
2
|
1
|
|
Part B Placebo-Controlled Withdrawal
Lost to Follow-up
|
0
|
1
|
0
|
Baseline Characteristics
A Two-Part, Single-Blind, Phase 3 Study Evaluating the Efficacy and Safety of Patiromer for the Treatment of Hyperkalemia (OPAL)
Baseline characteristics by cohort
| Measure |
Part A Patiromer
n=243 Participants
Participants were administered patiromer starting dose of 8.4 g or 16.8 g daily as a divided dose twice a day, orally, for 4 weeks.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
112 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
131 Participants
n=5 Participants
|
|
Age, Continuous
|
64.2 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
103 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
140 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Part A Baseline to Part A Week 4The primary analysis endpoint is the change from Baseline at Week 4. The estimate of the change at Week 4 is from a repeated measures model, which includes data from Weeks 1, 2, 3 and 4. The analysis includes all intent to treat participants who had a serum potassium result at baseline and at least one weekly post-baseline visit (i.e. Part A Week 1 or later) and excludes six participants who had no result collected after Day 3).
Outcome measures
| Measure |
Part A Patiromer
n=237 Participants
Participants were administered patiromer starting dose of 8.4 g or 16.8 g daily as a divided dose twice a day, orally, for 4 weeks.
|
Part B Patiromer
Participants continued on the same daily patiromer dose as administered at the time of the Part A Week 4 Visit for 8 weeks.
|
|---|---|---|
|
Change in Serum Potassium From Part A Baseline to Part A Week 4
|
-1.01 mEq/L
Standard Error 0.031
|
—
|
PRIMARY outcome
Timeframe: Part B Baseline to Part B Week 4 or first local laboratory serum potassium < 3.8 mEq/L or ≥ 5.5 mEq/LChange in Serum Potassium from Part B Baseline to either: Part B Week 4 visit, if the participant's serum potassium remained ≥ 3.8 mEq/L and \< 5.5 mEq/L up to the Part B Week 4 visit or the earliest Part B visit at which the participant's serum potassium was \< 3.8 mEq/L or ≥ 5.5 mEq/L.
Outcome measures
| Measure |
Part A Patiromer
n=52 Participants
Participants were administered patiromer starting dose of 8.4 g or 16.8 g daily as a divided dose twice a day, orally, for 4 weeks.
|
Part B Patiromer
n=55 Participants
Participants continued on the same daily patiromer dose as administered at the time of the Part A Week 4 Visit for 8 weeks.
|
|---|---|---|
|
Change in Serum Potassium From Part B Baseline
|
0.72 mEq/L
Interval 0.22 to 1.22
|
0 mEq/L
Interval -0.3 to 0.3
|
SECONDARY outcome
Timeframe: Week 4Population: Proportion of participants with serum potassium level in the target range at Part A Week 4
Outcome measures
| Measure |
Part A Patiromer
n=243 Participants
Participants were administered patiromer starting dose of 8.4 g or 16.8 g daily as a divided dose twice a day, orally, for 4 weeks.
|
Part B Patiromer
Participants continued on the same daily patiromer dose as administered at the time of the Part A Week 4 Visit for 8 weeks.
|
|---|---|---|
|
Proportion of Participants With Serum Potassium Levels in the Target Range of 3.8 to < 5.1 mEq/L at Part A Week 4
|
76 percentage of participants
Interval 70.0 to 81.0
|
—
|
SECONDARY outcome
Timeframe: Part B Baseline to Part B Week 8Outcome measures
| Measure |
Part A Patiromer
n=52 Participants
Participants were administered patiromer starting dose of 8.4 g or 16.8 g daily as a divided dose twice a day, orally, for 4 weeks.
|
Part B Patiromer
n=55 Participants
Participants continued on the same daily patiromer dose as administered at the time of the Part A Week 4 Visit for 8 weeks.
|
|---|---|---|
|
Proportion of Participants With Serum Potassium That Was ≥ 5.5 mEq/L in Part B
|
60 percentage of participants
|
15 percentage of participants
|
SECONDARY outcome
Timeframe: Part B Baseline to Part B Week 8Population: Percentages were estimated not as simple ratios, but by using a stratified method, in order to account for differences between the patiromer and placebo groups in terms of whether participants had type 2 diabetes mellitus and whether they entered the study with serum potassium \< 5.8 mEq/L or serum potassium ≥ 5.8 mEq/L.
Outcome measures
| Measure |
Part A Patiromer
n=52 Participants
Participants were administered patiromer starting dose of 8.4 g or 16.8 g daily as a divided dose twice a day, orally, for 4 weeks.
|
Part B Patiromer
n=55 Participants
Participants continued on the same daily patiromer dose as administered at the time of the Part A Week 4 Visit for 8 weeks.
|
|---|---|---|
|
Proportion of Participants With Serum Potassium ≥ 5.1 mEq/L in Part B
|
91 percentage of participants
|
43 percentage of participants
|
Adverse Events
Part A Patiromer
Serious events: 3 serious events
Other events: 33 other events
Deaths: 0 deaths
Part B Patiromer
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Part B Placebo
Serious events: 1 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Part A Patiromer
n=243 participants at risk
Participants were administered patiromer starting dose of 8.4 g or 16.8 g daily as a divided dose twice a day, orally, for 4 weeks.
|
Part B Patiromer
n=55 participants at risk
Participants continued on the same daily patiromer dose as administered at the time of the Part A Week 4 Visit for 8 weeks.
|
Part B Placebo
n=52 participants at risk
Participants were administered placebo orally twice a day for 8 weeks.
|
|---|---|---|---|
|
Investigations
Anticoagulation drug level below therapeutic
|
0.41%
1/243 • 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Participants who received at least one dose of trial medication
|
0.00%
0/55 • 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Participants who received at least one dose of trial medication
|
0.00%
0/52 • 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Participants who received at least one dose of trial medication
|
|
Cardiac disorders
Atrial fibrillation
|
0.41%
1/243 • 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Participants who received at least one dose of trial medication
|
0.00%
0/55 • 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Participants who received at least one dose of trial medication
|
0.00%
0/52 • 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Participants who received at least one dose of trial medication
|
|
Gastrointestinal disorders
Thrombosis mesenteric vessel
|
0.00%
0/243 • 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Participants who received at least one dose of trial medication
|
0.00%
0/55 • 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Participants who received at least one dose of trial medication
|
1.9%
1/52 • 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Participants who received at least one dose of trial medication
|
|
Renal and urinary disorders
Renal failure chronic
|
0.41%
1/243 • 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Participants who received at least one dose of trial medication
|
0.00%
0/55 • 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Participants who received at least one dose of trial medication
|
0.00%
0/52 • 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Participants who received at least one dose of trial medication
|
|
Infections and infestations
Escherichia bacteraemia
|
0.41%
1/243 • 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Participants who received at least one dose of trial medication
|
0.00%
0/55 • 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Participants who received at least one dose of trial medication
|
0.00%
0/52 • 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Participants who received at least one dose of trial medication
|
|
Infections and infestations
Urinary tract infection
|
0.41%
1/243 • 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Participants who received at least one dose of trial medication
|
0.00%
0/55 • 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Participants who received at least one dose of trial medication
|
0.00%
0/52 • 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Participants who received at least one dose of trial medication
|
|
Infections and infestations
Endocarditis enterococcal
|
0.41%
1/243 • 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Participants who received at least one dose of trial medication
|
0.00%
0/55 • 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Participants who received at least one dose of trial medication
|
0.00%
0/52 • 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Participants who received at least one dose of trial medication
|
Other adverse events
| Measure |
Part A Patiromer
n=243 participants at risk
Participants were administered patiromer starting dose of 8.4 g or 16.8 g daily as a divided dose twice a day, orally, for 4 weeks.
|
Part B Patiromer
n=55 participants at risk
Participants continued on the same daily patiromer dose as administered at the time of the Part A Week 4 Visit for 8 weeks.
|
Part B Placebo
n=52 participants at risk
Participants were administered placebo orally twice a day for 8 weeks.
|
|---|---|---|---|
|
Vascular disorders
Hypertension
|
1.6%
4/243 • 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Participants who received at least one dose of trial medication
|
0.00%
0/55 • 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Participants who received at least one dose of trial medication
|
5.8%
3/52 • 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Participants who received at least one dose of trial medication
|
|
Nervous system disorders
Headache
|
0.82%
2/243 • 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Participants who received at least one dose of trial medication
|
3.6%
2/55 • 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Participants who received at least one dose of trial medication
|
7.7%
4/52 • 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Participants who received at least one dose of trial medication
|
|
Gastrointestinal disorders
Constipation
|
10.7%
26/243 • 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Participants who received at least one dose of trial medication
|
3.6%
2/55 • 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Participants who received at least one dose of trial medication
|
0.00%
0/52 • 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Participants who received at least one dose of trial medication
|
|
Infections and infestations
Influenza
|
0.41%
1/243 • 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Participants who received at least one dose of trial medication
|
1.8%
1/55 • 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Participants who received at least one dose of trial medication
|
5.8%
3/52 • 2 weeks after Week 4 for Part A subjects who did not continue in Part B and 2 weeks after Week 12 for Part B.
Participants who received at least one dose of trial medication
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Our agreements generally provide that PI cannot publish single site data before publication of the multi-site publication, unless 1 year has elapsed since completion of the study at all sites. Thereafter, PI may publish provided that PI shall: provide a copy of the publication to sponsor at least 60 days in advance of submission for publication; delete sponsor's confidential information as requested; and delay publication up to an additional 90 days to permit protection of intellectual property.
- Publication restrictions are in place
Restriction type: OTHER