TOURMALINE: Patiromer With or Without Food for the Treatment of Hyperkalemia

• Sponsor: Relypsa, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02694744
• Collaborator: (none)
• Enrollment: 114
• Locations: 29
• Arms: 2
• Duration (Months): 6
• Patients Per Site: 3.9
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of patiromer administered once daily (QD) when given with food compared to without food (experimental treatment group) for the treatment of hyperkalemia (high potassium in the blood).

Condition or Disease	Intervention/Treatment	Phase
Hyperkalemia	Drug: patiromer	Phase 4

Detailed Description

Approximately 110 eligible participants with hyperkalemia will be randomly assigned to receive a patiromer starting dose of 8.4- g/day, either with or without food.

All participants will undergo a screening period (1 day) to determine eligibility for study entry. Eligible participants will be treated for 4 weeks and followed for 2 weeks after completing the patiromer treatment. There are six planned clinic visits during the Treatment Period and two planned visits after the last dose of patiromer during the Follow-up Period.

The dose of patiromer may be increased or decreased (titrated) based on participants' individual potassium response.

Study Design

• Study Type: Interventional
• Actual Enrollment: 114 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Effect of Food: An Open-Label, Randomized, Parallel Group Phase 4 Study of the Efficacy and Safety of Patiromer for Oral Suspension With or Without Food for the Treatment of Hyperkalemia (TOURMALINE)
• Study Start Date: Feb 1, 2016
• Actual Primary Completion Date: Jul 1, 2016
• Actual Study Completion Date: Aug 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 - Dosing Without Food Patiromer dosing without food	Drug: patiromer; 8.4 g/day starting dose, administered orally; Other Names: Veltassa RLY5016 for Oral Suspension
Active Comparator: Group 2 - Dosing With Food Patiromer dosing with food	Drug: patiromer; 8.4 g/day starting dose, administered orally; Other Names: Veltassa RLY5016 for Oral Suspension

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects With Serum Potassium in the Target Range (3.8 - 5.0 mEq/L) at Either Week 3 or Week 4 [21 to 28 Days]

Secondary Outcome Measures

1. Mean Change in Serum Potassium From Baseline to Week 4 [Baseline to Day 28]

   An ANCOVA model was used to estimate the mean serum potassium change from Baseline to Week 4 with baseline serum potassium as a covariate and treatment group, race (white vs all others), and history of Type 1 or 2 diabetes mellitus (yes or no) as factors in the model.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Potassium concentration > 5.0 mEq/L from two blood draws at Screening

• Stable RAASi medication, if taking

• Medications taken on a chronic basis are given once daily or twice daily

• Informed consent given

Key Exclusion Criteria:

• Expected need for dialysis

• Major organ transplant

• History of conditions associated with pseudohyperkalemia

• History of swallowing disorder, gastroparesis, bariatric surgery, bowel obstruction or severe gastrointestinal disorders or major gastrointestinal surgery

• Cancer or unstable medical condition

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigator Site 12	Fountain Valley	California	United States	92708
2	Investigator Site 11	Huntington Beach	California	United States	92648
3	Investigator Site 38	Palm Springs	California	United States	92262
4	Investigator Site 20	Riverside	California	United States	92505
5	Investigator Site 21	San Dimas	California	United States	91773
6	Investigator Site 24	Denver	Colorado	United States	80230
7	Investigator Site 30	Edgewater	Florida	United States	32132
8	Investigator Site 10	Hialeah	Florida	United States	33012
9	Investigator Site 13	Hollywood	Florida	United States	33021
10	Investigator Site 17	Lauderdale Lakes	Florida	United States	33313-1638
11	Investigator Site 16	Lauderdale Lakes	Florida	United States	33319
12	Investigator Site 15	Miami	Florida	United States	33015
13	Investigator Site 43	Miami	Florida	United States	33147
14	Investigator Site 18	Pembroke Pines	Florida	United States	33028
15	Investigator Site 27	Tampa	Florida	United States	33614
16	Investigator Site 44	Meridian	Idaho	United States	83642
17	Investigator Site 39	Aurora	Illinois	United States	60504
18	Investigator Site 23	Flint	Michigan	United States	48504
19	Investigator Site 34	Kansas City	Missouri	United States	64111
20	Investigator Site 41	Las Vegas	Nevada	United States	89106
21	Investigator Site 37	Flushing	New York	United States	11355
22	Investigator Site 36	Norman	Oklahoma	United States	73069
23	Investigator Site 40	Jackson	Tennessee	United States	38305
24	Investigator Site 33	Dallas	Texas	United States	75231
25	Investigator Site 26	San Antonio	Texas	United States	78202
26	Investigator Site 29	San Antonio	Texas	United States	78207
27	Investigator Site 28	San Antonio	Texas	United States	78215
28	Investigator Site 25	San Antonio	Texas	United States	78229
29	Investigator Site 22	Salt Lake City	Utah	United States	84124

Sponsors and Collaborators

• Relypsa, Inc.

Investigators

• Study Director: Study Director or VP Clinical Development, Relypsa, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Relypsa, Inc.
• ClinicalTrials.gov Identifier: NCT02694744
• Other Study ID Numbers: RLY5016-401
• First Posted: Feb 29, 2016
• Last Update Posted: May 12, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Relypsa, Inc.: Treatment of Hyperkalemia; Hyperkalemia; Potassium; Chronic Kidney Disease
• Additional relevant MeSH terms: Hyperkalemia

Study Results

Participant Flow

Arm/Group Title	Group 1 - Dosing Without Food	Group 2 - Dosing With Food
Arm/Group Description	Patiromer dosing without food patiromer: 8.4 g/day starting dose, administered orally	Patiromer dosing with food patiromer: 8.4 g/day starting dose, administered orally
Period Title: Overall Study
STARTED	57	57
Safety Population	57	56
ITT	57	55
COMPLETED	51	52
NOT COMPLETED	6	5

Baseline Characteristics

Arm/Group Title	Group 1 - Dosing Without Food	Group 2 - Dosing With Food	Total
Arm/Group Description	Patiromer dosing without food patiromer: 8.4 g/day starting dose, administered orally	Patiromer dosing with food patiromer: 8.4 g/day starting dose, administered orally *Note: Two randomized participants in Group 2 -Dosing With Food were excluded from the analyses for the intent-to-treat (ITT) population. One participant who did not receive any patiromer dose. Another participant had an important protocol violation and had no post-baseline serum K+, and was excluded from ITT prior to unblinding.	Total of all reporting groups
Overall Participants	57	55	112
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	19 33.3%	20 36.4%	39 34.8%
>=65 years	38 66.7%	35 63.6%	73 65.2%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	69	66	67
Sex: Female, Male (Count of Participants)
Female	17 29.8%	22 40%	39 34.8%
Male	40 70.2%	33 60%	73 65.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	33 57.9%	30 54.5%	63 56.3%
Not Hispanic or Latino	24 42.1%	25 45.5%	49 43.8%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	2 3.6%	2 1.8%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	6 10.5%	8 14.5%	14 12.5%
White	48 84.2%	44 80%	92 82.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	3 5.3%	1 1.8%	4 3.6%
Region of Enrollment (participants) [Number]
United States	57 100%	55 100%	112 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Subjects With Serum Potassium in the Target Range (3.8 - 5.0 mEq/L) at Either Week 3 or Week 4
Time Frame	21 to 28 Days

Outcome Measure Data

Analysis Population Description

The intent-to-treat (ITT) population for efficacy analyses includes all subjects who have been randomized and have taken at least one dose of patiromer.

Arm/Group Title	Group 1 - Dosing Without Food	Group 2 - Dosing With Food
Arm/Group Description	Patiromer dosing without food patiromer: 8.4 g/day starting dose, administered orally	Patiromer dosing with food patiromer: 8.4 g/day starting dose, administered orally
Measure Participants	57	55
Number (95% Confidence Interval) [percentage of participants]	82.5 144.7%	87.3 158.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1 - Dosing Without Food, Group 2 - Dosing With Food
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Other Statistical Analysis		If the 95% confidence interval for the w/out food Arm overlapped the confidence interval for the w/ food Arm, the study will conclude that there is no evidence of a statistically significant difference between treatment arms.

2. Secondary Outcome

Title	Mean Change in Serum Potassium From Baseline to Week 4
Description	An ANCOVA model was used to estimate the mean serum potassium change from Baseline to Week 4 with baseline serum potassium as a covariate and treatment group, race (white vs all others), and history of Type 1 or 2 diabetes mellitus (yes or no) as factors in the model.
Time Frame	Baseline to Day 28

Outcome Measure Data

Analysis Population Description

Only intent-to-treat subjects who were available at both Baseline and Week 4 visits.

Arm/Group Title	Group 1	Group 2
Arm/Group Description	Patiromer without Food	Patiromer with Food
Measure Participants	51	49
Least Squares Mean (Standard Error) [mEq/L]	-0.62 (0.094)	-0.65 (0.088)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 1 - Dosing Without Food, Group 2 - Dosing With Food
	Comments	Estimation of mean change in serum potassium from Baseline to week 4.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7893
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95%; -0.17 to 0.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Beginning from the time the subject signs the informed consent form until the subject's last study visit, up to 6 weeks.
Adverse Event Reporting Description	Treatment emergets AEs (TEAEs) and SAEs were coded in accordance with MedDRA version (18.1). A TEAE is defined as any AE that newly appeared or worsened in severity following initiation of study drug administration.
Arm/Group Title	Group 1 - Dosing Without Food		Group 2 - Dosing With Food
Arm/Group Description	Patiromer dosing without food patiromer: 8.4 g/day starting dose, administered orally		Patiromer dosing with food patiromer: 8.4 g/day starting dose, administered orally *Note - One randomized participant was excluded from the analysis as this participant did not receive any patiromer dose.
All Cause Mortality
	Group 1 - Dosing Without Food		Group 2 - Dosing With Food
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/57 (1.8%)		0/56 (0%)
Serious Adverse Events
	Group 1 - Dosing Without Food		Group 2 - Dosing With Food
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/57 (7%)		1/56 (1.8%)
Blood and lymphatic system disorders
Anaemia	1/57 (1.8%)		0/56 (0%)
Cardiac disorders
Angina pectoris	0/57 (0%)		1/56 (1.8%)
Cardio-respiratory arrest	1/57 (1.8%)		0/56 (0%)
Renal and urinary disorders
Acute kidney injury	1/57 (1.8%)		0/56 (0%)
Vascular disorders
Intermittent claudication	1/57 (1.8%)		0/56 (0%)
Other (Not Including Serious) Adverse Events
	Group 1 - Dosing Without Food		Group 2 - Dosing With Food
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/57 (7%)		8/56 (14.3%)
Gastrointestinal disorders
Diarrhoea	3/57 (5.3%)		3/56 (5.4%)
Investigations
Blood Creatine Phosphokinase Increased	1/57 (1.8%)		3/56 (5.4%)
Nervous system disorders
Headache	0/57 (0%)		3/56 (5.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.