Trial Outcomes & Findings for Evaluating Alternative Medical Therapies in Primary Hyperparathyroidism (NCT NCT02525796)
NCT ID: NCT02525796
Last Updated: 2023-05-03
Results Overview
Change in circulating PTH levels before and after 4 weeks of double-blinded intervention when compared to placebo
Recruitment status
COMPLETED
Study phase
PHASE2/PHASE3
Target enrollment
69 participants
Primary outcome timeframe
Change in circulating PTH levels before and after 4 weeks of double-blinded monotherapy intervention when compared to placebo (PTH at 4 weeks minus PTH at baseline)
Results posted on
2023-05-03
Participant Flow
Following enrollment (n=69), participants underwent medication washout to eliminate interference with renin-angiotensin-aldosterone system measurements. ACE inhibitors, ARBs, ENaC inhibitors, and MR antagonists were stopped for 2 weeks and BP controlled with alternative agents, if needed. During washout, 28 participants were withdrawn, thus the number of participants at the time of randomization to monotherapy was 41. 36 of 41 completed 4wks and began the cinacalcet open-label phase.
Participant milestones
| Measure |
Eplerenone
Patients with primary hyperparathyroidism will receive maximally-tolerated, double-blinded, eplerenone monotherapy for 4 weeks, followed by an open-label extension wherein maximally-tolerated cinacalcet therapy will be added to eplerenone for 2 weeks.
|
Amiloride
Patients with primary hyperparathyroidism will receive maximally-tolerated, double-blinded, amiloride monotherapy for 4 weeks, , followed by an open-label extension wherein maximally-tolerated cinacalcet therapy will be added to amiloride for 2 weeks.
|
Placebo
Patients with primary hyperparathyroidism will receive maximally-tolerated, double-blinded, placebo monotherapy for 4 weeks, followed by an open-label extension wherein maximally-tolerated cinacalcet therapy will be added to placebo for 2 weeks.
|
|---|---|---|---|
|
Randomization to Monotherapy for 4 Weeks
STARTED
|
14
|
14
|
13
|
|
Randomization to Monotherapy for 4 Weeks
COMPLETED
|
12
|
12
|
12
|
|
Randomization to Monotherapy for 4 Weeks
NOT COMPLETED
|
2
|
2
|
1
|
|
Open-label Addition of Cinacalcet
STARTED
|
12
|
12
|
12
|
|
Open-label Addition of Cinacalcet
Open-label Cinacalcet
|
12
|
12
|
12
|
|
Open-label Addition of Cinacalcet
COMPLETED
|
8
|
10
|
9
|
|
Open-label Addition of Cinacalcet
NOT COMPLETED
|
4
|
2
|
3
|
Reasons for withdrawal
| Measure |
Eplerenone
Patients with primary hyperparathyroidism will receive maximally-tolerated, double-blinded, eplerenone monotherapy for 4 weeks, followed by an open-label extension wherein maximally-tolerated cinacalcet therapy will be added to eplerenone for 2 weeks.
|
Amiloride
Patients with primary hyperparathyroidism will receive maximally-tolerated, double-blinded, amiloride monotherapy for 4 weeks, , followed by an open-label extension wherein maximally-tolerated cinacalcet therapy will be added to amiloride for 2 weeks.
|
Placebo
Patients with primary hyperparathyroidism will receive maximally-tolerated, double-blinded, placebo monotherapy for 4 weeks, followed by an open-label extension wherein maximally-tolerated cinacalcet therapy will be added to placebo for 2 weeks.
|
|---|---|---|---|
|
Randomization to Monotherapy for 4 Weeks
Adverse Event
|
1
|
1
|
1
|
|
Randomization to Monotherapy for 4 Weeks
Lost to Follow-up
|
1
|
0
|
0
|
|
Randomization to Monotherapy for 4 Weeks
Physician Decision
|
0
|
1
|
0
|
|
Open-label Addition of Cinacalcet
Withdrawal by Subject
|
2
|
0
|
1
|
|
Open-label Addition of Cinacalcet
Adverse Event
|
2
|
2
|
2
|
Baseline Characteristics
Evaluating Alternative Medical Therapies in Primary Hyperparathyroidism
Baseline characteristics by cohort
| Measure |
Eplerenone
n=14 Participants
Patients with primary hyperparathyroidism will receive maximally-tolerated eplerenone for 4 weeks
|
Amiloride
n=14 Participants
Patients with primary hyperparathyroidism will receive maximally-tolerated amiloride for 4 weeks
|
Placebo
n=13 Participants
Patients with primary hyperparathyroidism will receive placebo for 4 weeks
|
Total
n=41 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
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
7 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
19 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
7 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
22 Participants
n=4 Participants
|
|
Age, Continuous
|
65 years
STANDARD_DEVIATION 7 • n=5 Participants
|
61 years
STANDARD_DEVIATION 9 • n=7 Participants
|
69 years
STANDARD_DEVIATION 10 • n=5 Participants
|
65 years
STANDARD_DEVIATION 9 • n=4 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
34 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
12 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
31 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
14 participants
n=5 Participants
|
14 participants
n=7 Participants
|
13 participants
n=5 Participants
|
41 participants
n=4 Participants
|
|
Parathyroid hormone
|
65 pg/mL
STANDARD_DEVIATION 17 • n=5 Participants
|
89 pg/mL
STANDARD_DEVIATION 56 • n=7 Participants
|
66 pg/mL
STANDARD_DEVIATION 26 • n=5 Participants
|
74 pg/mL
STANDARD_DEVIATION 39 • n=4 Participants
|
|
Serum calcium
|
10.4 mg/dL
STANDARD_DEVIATION 0.5 • n=5 Participants
|
10.5 mg/dL
STANDARD_DEVIATION 0.5 • n=7 Participants
|
10.4 mg/dL
STANDARD_DEVIATION 0.6 • n=5 Participants
|
10.5 mg/dL
STANDARD_DEVIATION 0.5 • n=4 Participants
|
PRIMARY outcome
Timeframe: Change in circulating PTH levels before and after 4 weeks of double-blinded monotherapy intervention when compared to placebo (PTH at 4 weeks minus PTH at baseline)Population: Number of participants who completed the 4 week double-blinded monotherapy intervention
Change in circulating PTH levels before and after 4 weeks of double-blinded intervention when compared to placebo
Outcome measures
| Measure |
Eplerenone
n=12 Participants
Patients with primary hyperparathyroidism will receive maximally-tolerated eplerenone monotherapy for 4 weeks
|
Amiloride
n=12 Participants
Patients with primary hyperparathyroidism will receive maximally-tolerated amiloride monotherapy for 4 weeks
|
Placebo
n=12 Participants
Patients with primary hyperparathyroidism will receive placebo monotherapy for 4 weeks
|
|---|---|---|---|
|
Change in Parathyroid Hormone Levels
|
4.0 pg/mL
Interval -10.4 to 10.4
|
-3.7 pg/mL
Interval -11.4 to 8.7
|
0.8 pg/mL
Interval -3.6 to 8.3
|
SECONDARY outcome
Timeframe: Change in serum calcium levels before and after 4 weeks of double-blinded monotherapy intervention when compared to placebo (calcium at 4 weeks minus calcium at baseline)Population: patients with primary hyperparathyroidism receiving double-blinded monotherapy for 4 weeks
Change in serum calcium levels before and after intervention when compared to placebo
Outcome measures
| Measure |
Eplerenone
n=12 Participants
Patients with primary hyperparathyroidism will receive maximally-tolerated eplerenone monotherapy for 4 weeks
|
Amiloride
n=12 Participants
Patients with primary hyperparathyroidism will receive maximally-tolerated amiloride monotherapy for 4 weeks
|
Placebo
n=12 Participants
Patients with primary hyperparathyroidism will receive placebo monotherapy for 4 weeks
|
|---|---|---|---|
|
Change in Calcium Levels
|
0.1 mg/dL
Interval -0.1 to 3.0
|
0.0 mg/dL
Interval -0.3 to 0.1
|
0.1 mg/dL
Interval -0.1 to 0.4
|
Adverse Events
Eplerenone
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Amiloride
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Eplerenone + Cinacalcet
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Amiloride + Cinacalcet
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Placebo + Cinacalcet
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Eplerenone
n=14 participants at risk
Patients with primary hyperparathyroidism will receive maximally-tolerated eplerenone for 4 weeks
|
Amiloride
n=14 participants at risk
Patients with primary hyperparathyroidism will receive maximally-tolerated amiloride for 4 weeks
|
Placebo
n=13 participants at risk
Patients with primary hyperparathyroidism will receive placebo for 4 weeks
|
Eplerenone + Cinacalcet
n=12 participants at risk
Open-label cinacalcet added for 2 weeks
|
Amiloride + Cinacalcet
n=12 participants at risk
Open-label cinacalcet added for 2 weeks
|
Placebo + Cinacalcet
n=12 participants at risk
Open-label cinacalcet added for 2 weeks
|
|---|---|---|---|---|---|---|
|
Renal and urinary disorders
low egfr
|
0.00%
0/14 • Over the course of the entire study, including the 4 week randomization to monotherapy (eplerenone vs amiloride vs placebo) and the 2 week open-label addition of cinacalcet (6 weeks in total).
same as clinicaltrials.gov
|
0.00%
0/14 • Over the course of the entire study, including the 4 week randomization to monotherapy (eplerenone vs amiloride vs placebo) and the 2 week open-label addition of cinacalcet (6 weeks in total).
same as clinicaltrials.gov
|
7.7%
1/13 • Number of events 1 • Over the course of the entire study, including the 4 week randomization to monotherapy (eplerenone vs amiloride vs placebo) and the 2 week open-label addition of cinacalcet (6 weeks in total).
same as clinicaltrials.gov
|
8.3%
1/12 • Number of events 1 • Over the course of the entire study, including the 4 week randomization to monotherapy (eplerenone vs amiloride vs placebo) and the 2 week open-label addition of cinacalcet (6 weeks in total).
same as clinicaltrials.gov
|
0.00%
0/12 • Over the course of the entire study, including the 4 week randomization to monotherapy (eplerenone vs amiloride vs placebo) and the 2 week open-label addition of cinacalcet (6 weeks in total).
same as clinicaltrials.gov
|
0.00%
0/12 • Over the course of the entire study, including the 4 week randomization to monotherapy (eplerenone vs amiloride vs placebo) and the 2 week open-label addition of cinacalcet (6 weeks in total).
same as clinicaltrials.gov
|
|
General disorders
hyperkalemia
|
7.1%
1/14 • Number of events 1 • Over the course of the entire study, including the 4 week randomization to monotherapy (eplerenone vs amiloride vs placebo) and the 2 week open-label addition of cinacalcet (6 weeks in total).
same as clinicaltrials.gov
|
7.1%
1/14 • Number of events 1 • Over the course of the entire study, including the 4 week randomization to monotherapy (eplerenone vs amiloride vs placebo) and the 2 week open-label addition of cinacalcet (6 weeks in total).
same as clinicaltrials.gov
|
0.00%
0/13 • Over the course of the entire study, including the 4 week randomization to monotherapy (eplerenone vs amiloride vs placebo) and the 2 week open-label addition of cinacalcet (6 weeks in total).
same as clinicaltrials.gov
|
0.00%
0/12 • Over the course of the entire study, including the 4 week randomization to monotherapy (eplerenone vs amiloride vs placebo) and the 2 week open-label addition of cinacalcet (6 weeks in total).
same as clinicaltrials.gov
|
8.3%
1/12 • Number of events 1 • Over the course of the entire study, including the 4 week randomization to monotherapy (eplerenone vs amiloride vs placebo) and the 2 week open-label addition of cinacalcet (6 weeks in total).
same as clinicaltrials.gov
|
8.3%
1/12 • Number of events 1 • Over the course of the entire study, including the 4 week randomization to monotherapy (eplerenone vs amiloride vs placebo) and the 2 week open-label addition of cinacalcet (6 weeks in total).
same as clinicaltrials.gov
|
|
Endocrine disorders
hypocalcemia
|
0.00%
0/14 • Over the course of the entire study, including the 4 week randomization to monotherapy (eplerenone vs amiloride vs placebo) and the 2 week open-label addition of cinacalcet (6 weeks in total).
same as clinicaltrials.gov
|
0.00%
0/14 • Over the course of the entire study, including the 4 week randomization to monotherapy (eplerenone vs amiloride vs placebo) and the 2 week open-label addition of cinacalcet (6 weeks in total).
same as clinicaltrials.gov
|
0.00%
0/13 • Over the course of the entire study, including the 4 week randomization to monotherapy (eplerenone vs amiloride vs placebo) and the 2 week open-label addition of cinacalcet (6 weeks in total).
same as clinicaltrials.gov
|
8.3%
1/12 • Number of events 1 • Over the course of the entire study, including the 4 week randomization to monotherapy (eplerenone vs amiloride vs placebo) and the 2 week open-label addition of cinacalcet (6 weeks in total).
same as clinicaltrials.gov
|
0.00%
0/12 • Over the course of the entire study, including the 4 week randomization to monotherapy (eplerenone vs amiloride vs placebo) and the 2 week open-label addition of cinacalcet (6 weeks in total).
same as clinicaltrials.gov
|
8.3%
1/12 • Number of events 1 • Over the course of the entire study, including the 4 week randomization to monotherapy (eplerenone vs amiloride vs placebo) and the 2 week open-label addition of cinacalcet (6 weeks in total).
same as clinicaltrials.gov
|
|
Cardiac disorders
low blood pressure
|
0.00%
0/14 • Over the course of the entire study, including the 4 week randomization to monotherapy (eplerenone vs amiloride vs placebo) and the 2 week open-label addition of cinacalcet (6 weeks in total).
same as clinicaltrials.gov
|
0.00%
0/14 • Over the course of the entire study, including the 4 week randomization to monotherapy (eplerenone vs amiloride vs placebo) and the 2 week open-label addition of cinacalcet (6 weeks in total).
same as clinicaltrials.gov
|
0.00%
0/13 • Over the course of the entire study, including the 4 week randomization to monotherapy (eplerenone vs amiloride vs placebo) and the 2 week open-label addition of cinacalcet (6 weeks in total).
same as clinicaltrials.gov
|
0.00%
0/12 • Over the course of the entire study, including the 4 week randomization to monotherapy (eplerenone vs amiloride vs placebo) and the 2 week open-label addition of cinacalcet (6 weeks in total).
same as clinicaltrials.gov
|
8.3%
1/12 • Number of events 1 • Over the course of the entire study, including the 4 week randomization to monotherapy (eplerenone vs amiloride vs placebo) and the 2 week open-label addition of cinacalcet (6 weeks in total).
same as clinicaltrials.gov
|
0.00%
0/12 • Over the course of the entire study, including the 4 week randomization to monotherapy (eplerenone vs amiloride vs placebo) and the 2 week open-label addition of cinacalcet (6 weeks in total).
same as clinicaltrials.gov
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place