Trial Outcomes & Findings for Evaluation of Patiromer in Heart Failure Patients (NCT NCT00868439)

NCT ID: NCT00868439

Last Updated: 2021-06-02

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 120 participants
• Primary outcome timeframe: Baseline and Day 28
• Results posted on: 2021-06-02

Participant Flow

120 subjects were randomized in Part 1 of the study (60 to each treatment group). Of these, 120 randomized subjects, 105 received either RLY5016 Powder for Suspension (n = 56) or placebo (n = 49).

Eligible participants ≥ 18 y/o, had history of chronic HF, clinically initiated spironolactone therapy, serum K+ = 4.3 - 5.1 mEq/L at screening and baseline, and either had 1) CKD, w/ eGFR < 60 mL/min and receiving HF therapies or 2) documented history of hyperkalemia led to discontinuation w/ aldosterone antagonist w/in 6 months prior to baseline.

Participant milestones

Measure	Patiromer Spironolactone + Patiromer Participants received patiromer (15 g twice daily \[BID\]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was \> 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was \> 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or \> 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.	Placebo Spironolactone + Placebo Participants received placebo (twice daily \[BID\]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was \> 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was \> 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or \> 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.
Overall Study STARTED	56	49
Overall Study COMPLETED	48	40
Overall Study NOT COMPLETED	8	9

Reasons for withdrawal

Measure	Patiromer Spironolactone + Patiromer Participants received patiromer (15 g twice daily \[BID\]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was \> 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was \> 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or \> 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.	Placebo Spironolactone + Placebo Participants received placebo (twice daily \[BID\]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was \> 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was \> 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or \> 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.
Overall Study Adverse Event	4	3
Overall Study Prot-Specified W/D Criteria (Serum K+)	2	3
Overall Study Death	0	1
Overall Study Protocol Violation	1	1
Overall Study Physician Decision	1	0
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Evaluation of Patiromer in Heart Failure Patients

Baseline characteristics by cohort

Measure	Patiromer n=55 Participants Spironolactone + Patiromer Participants received patiromer (15 g twice daily \[BID\]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was \> 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was \> 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or \> 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.	Placebo n=49 Participants Spironolactone + Placebo Participants received placebo (twice daily \[BID\]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was \> 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was \> 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or \> 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.	Total n=104 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	16 Participants n=5 Participants	14 Participants n=7 Participants	30 Participants n=5 Participants
Age, Categorical >=65 years	39 Participants n=5 Participants	35 Participants n=7 Participants	74 Participants n=5 Participants
Age, Continuous	68.3 years STANDARD_DEVIATION 8.66 • n=5 Participants	68.2 years STANDARD_DEVIATION 10.46 • n=7 Participants	68.3 years STANDARD_DEVIATION 9.50 • n=5 Participants
Sex: Female, Male Female	26 Participants n=5 Participants	15 Participants n=7 Participants	41 Participants n=5 Participants
Sex: Female, Male Male	29 Participants n=5 Participants	34 Participants n=7 Participants	63 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Day 28

Population: Analysis was determined using Last Observation Carried Forward (LOCF).

Outcome measures

Measure	Patiromer n=55 Participants Spironolactone + Patiromer Participants received patiromer (15 g twice daily \[BID\]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was \> 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was \> 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or \> 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.	Placebo n=49 Participants Spironolactone + Placebo Participants received placebo (twice daily \[BID\]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was \> 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was \> 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or \> 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.
Change From Baseline in Serum Potassium to the End of the 28-day Treatment Period.	-0.21 mEq/L Standard Error 0.066	0.23 mEq/L Standard Error 0.072

SECONDARY outcome

Timeframe: 28 Days

Analysis based on central laboratory data.

Outcome measures

Measure	Patiromer n=55 Participants Spironolactone + Patiromer Participants received patiromer (15 g twice daily \[BID\]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was \> 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was \> 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or \> 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.	Placebo n=49 Participants Spironolactone + Placebo Participants received placebo (twice daily \[BID\]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was \> 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was \> 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or \> 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.
Proportion of Participants With a Serum Potassium Level During the 28-day Treatment Period That Was > 5.5 mEq/L.	7.3 percentage of participants	24.5 percentage of participants

SECONDARY outcome

Timeframe: 28 Days

Analysis based on local laboratory data.

Outcome measures

Measure	Patiromer n=55 Participants Spironolactone + Patiromer Participants received patiromer (15 g twice daily \[BID\]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was \> 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was \> 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or \> 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.	Placebo n=49 Participants Spironolactone + Placebo Participants received placebo (twice daily \[BID\]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was \> 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was \> 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or \> 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.
Proportion of Participants Discontinuing the Study Due to Serum Potassium Elevation (Serum K+ > 5.5 mEq/L).	0 percentage of participants	6.1 percentage of participants

SECONDARY outcome

Timeframe: 28 Days

Outcome measures

Measure	Patiromer n=55 Participants Spironolactone + Patiromer Participants received patiromer (15 g twice daily \[BID\]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was \> 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was \> 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or \> 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.	Placebo n=49 Participants Spironolactone + Placebo Participants received placebo (twice daily \[BID\]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was \> 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was \> 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or \> 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.
Proportion of Participants Whose Spironolactone Dose Was Increased.	90.9 percentage of participants	73.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Day 28

Population: Analysis was determined using LOCF.

Outcome measures

Measure	Patiromer n=55 Participants Spironolactone + Patiromer Participants received patiromer (15 g twice daily \[BID\]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was \> 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was \> 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or \> 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.	Placebo n=49 Participants Spironolactone + Placebo Participants received placebo (twice daily \[BID\]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was \> 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was \> 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or \> 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.
Proportion of Participants With an Increase in Serum Potassium Level From Baseline to the End of the 28-day Treatment Period That Was ≥ 0.5 mEq/L	12.7 percentage of participants	24.5 percentage of participants

SECONDARY outcome

Timeframe: 28 Days

Outcome measures

Measure	Patiromer n=55 Participants Spironolactone + Patiromer Participants received patiromer (15 g twice daily \[BID\]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was \> 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was \> 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or \> 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.	Placebo n=49 Participants Spironolactone + Placebo Participants received placebo (twice daily \[BID\]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was \> 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was \> 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or \> 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.
Time to First Elevated Serum K+ > 5.5 mEq/L.	NA days Median time for first occurrence of serum potassium \> 5.5 mEq/L was not reached.	NA days Median time for first occurrence of serum potassium \> 5.5 mEq/L was not reached.

Adverse Events

Patiromer

Serious events: 2 serious events

Other events: 11 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Measure	Patiromer n=56 participants at risk Spironolactone + Patiromer Participants received patiromer (15 g twice daily \[BID\]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was \> 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was \> 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or \> 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.	Placebo n=49 participants at risk Spironolactone + Placebo Participants received placebo (twice daily \[BID\]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was \> 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was \> 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or \> 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.
Metabolism and nutrition disorders Gout	0.00% 0/56 • Up to 7 days after Day 28 or last patiromer dose, whichever was earlier. Randomized participants who received at least one dose of trial medication.	2.0% 1/49 • Up to 7 days after Day 28 or last patiromer dose, whichever was earlier. Randomized participants who received at least one dose of trial medication.
Cardiac disorders Coronary artery disease	3.6% 2/56 • Up to 7 days after Day 28 or last patiromer dose, whichever was earlier. Randomized participants who received at least one dose of trial medication.	0.00% 0/49 • Up to 7 days after Day 28 or last patiromer dose, whichever was earlier. Randomized participants who received at least one dose of trial medication.
Cardiac disorders Acute myocardial infarction	1.8% 1/56 • Up to 7 days after Day 28 or last patiromer dose, whichever was earlier. Randomized participants who received at least one dose of trial medication.	0.00% 0/49 • Up to 7 days after Day 28 or last patiromer dose, whichever was earlier. Randomized participants who received at least one dose of trial medication.
Cardiac disorders Atrial fibrillation	1.8% 1/56 • Up to 7 days after Day 28 or last patiromer dose, whichever was earlier. Randomized participants who received at least one dose of trial medication.	0.00% 0/49 • Up to 7 days after Day 28 or last patiromer dose, whichever was earlier. Randomized participants who received at least one dose of trial medication.
General disorders Sudden cardiac death	0.00% 0/56 • Up to 7 days after Day 28 or last patiromer dose, whichever was earlier. Randomized participants who received at least one dose of trial medication.	2.0% 1/49 • Up to 7 days after Day 28 or last patiromer dose, whichever was earlier. Randomized participants who received at least one dose of trial medication.

Other adverse events

Measure	Patiromer n=56 participants at risk Spironolactone + Patiromer Participants received patiromer (15 g twice daily \[BID\]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was \> 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was \> 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or \> 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.	Placebo n=49 participants at risk Spironolactone + Placebo Participants received placebo (twice daily \[BID\]). Participants also started spironolactone at a dose of 25 mg/day, which was increased to 50 mg/day after 2 weeks if the participant's serum potassium (based on local laboratory determination) was \> 3.5 mEq/L and ≤ 5.1 mEq/L. The spironolactone dose remained at 25 mg/day if the serum potassium was \> 5.1 mEq/L and ≤ 5.5 mEq/L. If, at any time, a participant's serum potassium level was confirmed to be ≤ 3.5 mEq/L or \> 5.5 mEq/L based on local laboratory data, the participant was to be discontinued from the study.
Gastrointestinal disorders Constipation	5.4% 3/56 • Up to 7 days after Day 28 or last patiromer dose, whichever was earlier. Randomized participants who received at least one dose of trial medication.	0.00% 0/49 • Up to 7 days after Day 28 or last patiromer dose, whichever was earlier. Randomized participants who received at least one dose of trial medication.
Gastrointestinal disorders Diarrhoea	5.4% 3/56 • Up to 7 days after Day 28 or last patiromer dose, whichever was earlier. Randomized participants who received at least one dose of trial medication.	2.0% 1/49 • Up to 7 days after Day 28 or last patiromer dose, whichever was earlier. Randomized participants who received at least one dose of trial medication.
Gastrointestinal disorders Flatulence	7.1% 4/56 • Up to 7 days after Day 28 or last patiromer dose, whichever was earlier. Randomized participants who received at least one dose of trial medication.	0.00% 0/49 • Up to 7 days after Day 28 or last patiromer dose, whichever was earlier. Randomized participants who received at least one dose of trial medication.
Investigations Blood urea increased	5.4% 3/56 • Up to 7 days after Day 28 or last patiromer dose, whichever was earlier. Randomized participants who received at least one dose of trial medication.	0.00% 0/49 • Up to 7 days after Day 28 or last patiromer dose, whichever was earlier. Randomized participants who received at least one dose of trial medication.

Additional Information

Medical Information

Relypsa, Inc.

Phone: 1-844-relypsa

Email: medinfo@relypsa.com

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