Dose Finding Study to Treat High Phosphate Levels in the Blood.
Sponsor
Ardelyx (Industry)
Overall Status
Completed
CT.gov ID
NCT02081534
Collaborator
(none)
162
41
7
8
4
0.5
Study Details
Study Description
Brief Summary
Randomized. double blind, placebo controlled, parallel arms dose finding study with a 4 weeks treatment period
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
The study consists of a screening period of approximately 1 week, a wash out period of up to 3 weeks, where existing phosphate lowering medication is withheld, a 4-week treatment period and a follow-up period of up to 2 weeks, during which patients are put back on their pre washout phosphate lowering medication.
The wash out period will be either 1 week, 2 weeks or 3 weeks depending on the increase in s-phosphate levels.
There are 7 parallel treatment arms in the study with bid and od treatment regimens.
Laboratory efficacy endpoints and safety assessments will be evaluated at various times throughout the study.
The target population of the study is: male or female patients, above18 years of age with End Stage Renal Disease (ESRD) on chronic maintenance hemodialysis (HD) 3 times a week for a minimum of 3 months.
Study Design
Study Type:
Interventional
Actual Enrollment
:
162 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase 2b, Randomized, Double Blind, Placebo-controlled, Parallel Group, Multicentre Dose Finding Study to Evaluate the Efficacy, Safety and Tolerability of AZD1722 to Treat Hyperphosphatemia in End-Stage Renal Disease Patients on Hemodialysis (ESRD-HD)
Study Start Date
:
Mar 1, 2014
Actual Primary Completion Date
:
Nov 1, 2014
Actual Study Completion Date
:
Nov 1, 2014
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 1 mg bid 1 mg AZD1722 bid |
Drug: AZD1722
AZD1722, oral tablet
|
| Experimental: 3 mg bid 3 mg AZD1722 bid |
Drug: AZD1722
AZD1722, oral tablet
|
| Experimental: 10 mg bid 10 mg AZD1722 bid |
Drug: AZD1722
AZD1722, oral tablet
|
| Experimental: 30 mg bid 30 mg AZD1722 bid |
Drug: AZD1722
AZD1722, oral tablet
|
| Experimental: 3 mg od 3 mg AZD1722 od |
Drug: AZD1722
AZD1722, oral tablet
|
| Experimental: 30 mg od 30 mg AZD1722 od |
Drug: AZD1722
AZD1722, oral tablet
|
| Placebo Comparator: Placebo Placebo (double dummy technique) |
Drug: Placebo
Placebo bid, double dummy technique
|
Outcome Measures
Primary Outcome Measures
- Change in Serum Phosphate Levels [End of wash out (pre randomization value) to end of treatment (Day 29)]
Change in serum phosphate levels from the end of wash out (pre randomization value) to end of treatment
Secondary Outcome Measures
- Change From Baseline in Calcium x Phosphorus Product [End of wash out (pre randomization value) to end of treatment (Day 29)]
Change from baseline (end of wash out) in calcium x phosphorus product
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 85 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Females and males aged ≥18 years
-
Chronic maintenance hemodialysis 3 x/week for a at least 3 months
-
Prescribed and taking at least 3 doses of phosphate binder per day
-
Serum phosphate levels should be between 3.5 and 8.0 mg/dL ; 1.13 mmol/L and 2.58 mmol/L (inclusive) at screening
-
Total serum calcium levels 2.0 - 2.6 mmol/L inclusive at screening
-
For randomization in the study, after up to 3 weeks wash out of phosphate binders, patients must have serum phosphate levels of at least 6. 0 mg/dL (1.94 mmol/L) but below 10 mg/dL (3.23 mmol/L) and have had an increase of at least 1.5 mg/dL (0.48 mmol/L) vs pre wash out
Exclusion Criteria:
-
Severe hyperphosphatemia defined as >10 mg/dL on Phosphate-binders at all time points during clinical routine monitoring for the 3 preceding months before screening visit.
-
Serum parathyroid hormone >1200 pg/mL
-
Significant metabolic acidosis
-
Clinical signs of hypovolemia at randomization
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Site | Downey | California | United States | |
| 2 | Research Site | Los Angeles | California | United States | |
| 3 | Research Site | Sacramento | California | United States | |
| 4 | Research Site | Whittier | California | United States | |
| 5 | Research Site | Denver | Colorado | United States | |
| 6 | Research Site | Pembroke Pines | Florida | United States | |
| 7 | Research Site | Tampa | Florida | United States | |
| 8 | Research Site | Winter Park | Florida | United States | |
| 9 | Research Site | Springfield | Massachusetts | United States | |
| 10 | Research Site | Detroit | Michigan | United States | |
| 11 | Research Site | Voorhees | New Jersey | United States | |
| 12 | Research Site | Flushing | New York | United States | |
| 13 | Research Site | Maspeth | New York | United States | |
| 14 | Research Site | Charlotte | North Carolina | United States | |
| 15 | Research Site | Cincinnati | Ohio | United States | |
| 16 | Research Site | San Antonio | Texas | United States | |
| 17 | Research Site | Bialystok | Poland | ||
| 18 | Research Site | Czestochowa | Poland | ||
| 19 | Research Site | Dzialdowo | Poland | ||
| 20 | Research Site | Legnica | Poland | ||
| 21 | Research Site | Lublin | Poland | ||
| 22 | Research Site | Radom | Poland | ||
| 23 | Research Site | Szczecin | Poland | ||
| 24 | Research Site | Warszawa | Poland | ||
| 25 | Research Site | Wroclaw | Poland | ||
| 26 | Research Site | Zamosc | Poland | ||
| 27 | Research Site | Zary | Poland | ||
| 28 | Research Site | Zgierz | Poland | ||
| 29 | Research Site | Banska Bystrica | Slovakia | ||
| 30 | Research Site | Bratislava | Slovakia | ||
| 31 | Research Site | Hlohovec | Slovakia | ||
| 32 | Research Site | Kosice | Slovakia | ||
| 33 | Research Site | Piestany | Slovakia | ||
| 34 | Research Site | Puchov | Slovakia | ||
| 35 | Research Site | Senica | Slovakia | ||
| 36 | Research Site | Birmingham | United Kingdom | ||
| 37 | Research Site | Doncaster | United Kingdom | ||
| 38 | Research Site | Exeter | United Kingdom | ||
| 39 | Research Site | Hull | United Kingdom | ||
| 40 | Research Site | Leicester | United Kingdom | ||
| 41 | Research Site | London | United Kingdom |
Sponsors and Collaborators
- Ardelyx
Investigators
- Principal Investigator: Geoffrey A Block, MD, Denver Nephrology PC, Denver, CO 80230
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Ardelyx
ClinicalTrials.gov Identifier:
NCT02081534
Other Study ID Numbers:
- D5613C00001
First Posted:
Mar 7, 2014
Last Update Posted:
Sep 14, 2020
Last Verified:
Aug 1, 2020
Keywords provided by Ardelyx
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | 1 mg Bid | 3 mg Bid | 10 mg Bid | 30 mg Bid | 3 mg od | 30 mg od | Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | 1 mg AZD1722 bid AZD1722: tenapanor, oral tablet | 3 mg AZD1722 bid AZD1722: tenapanor, oral tablet | 10 mg AZD1722 bid AZD1722: tenapanor, oral tablet | 30 mg AZD1722 bid AZD1722: tenapanor, oral tablet | 3 mg AZD1722 od AZD1722: tenapanor, oral tablet | 30 mg AZD1722 od AZD1722: tenapanor, oral tablet | Placebo (double dummy technique) Placebo: Placebo bid, double dummy technique |
| Period Title: Overall Study | |||||||
| STARTED | 23 | 21 | 23 | 26 | 22 | 21 | 26 |
| COMPLETED | 18 | 13 | 19 | 13 | 18 | 12 | 22 |
| NOT COMPLETED | 5 | 8 | 4 | 13 | 4 | 9 | 4 |
Baseline Characteristics
| Arm/Group Title | 1 mg Bid | 3 mg Bid | 10 mg Bid | 30 mg Bid | 3 mg od | 30 mg od | Placebo | Total |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | 1 mg AZD1722 bid AZD1722: tenapanor, oral tablet | 3 mg AZD1722 bid AZD1722: tenapanor, oral tablet | 10 mg AZD1722 bid AZD1722: tenapanor, oral tablet | 30 mg AZD1722 bid AZD1722: tenapanor, oral tablet | 3 mg AZD1722 od AZD1722: tenapanor, oral tablet | 30 mg AZD1722 od AZD1722: tenapanor, oral tablet | Placebo (double dummy technique) Placebo: Placebo bid, double dummy technique | Total of all reporting groups |
| Overall Participants | 23 | 21 | 23 | 26 | 22 | 21 | 26 | 162 |
| Age (years) [Mean (Standard Deviation) ] | ||||||||
| Mean (Standard Deviation) [years] |
57.9
(14.79)
|
61.5
(11.21)
|
62.7
(12.53)
|
59.7
(12.96)
|
57.6
(15.78)
|
58.2
(15.75)
|
56.1
(13.14)
|
59.1
(14.1)
|
| Sex: Female, Male (Count of Participants) | ||||||||
| Female |
16
69.6%
|
15
71.4%
|
15
65.2%
|
17
65.4%
|
12
54.5%
|
13
61.9%
|
16
61.5%
|
104
64.2%
|
| Male |
7
30.4%
|
6
28.6%
|
8
34.8%
|
9
34.6%
|
10
45.5%
|
8
38.1%
|
10
38.5%
|
58
35.8%
|
| Ethnicity (NIH/OMB) (Count of Participants) | ||||||||
| Hispanic or Latino |
7
30.4%
|
7
33.3%
|
10
43.5%
|
4
15.4%
|
8
36.4%
|
6
28.6%
|
6
23.1%
|
48
29.6%
|
| Not Hispanic or Latino |
16
69.6%
|
14
66.7%
|
13
56.5%
|
22
84.6%
|
14
63.6%
|
15
71.4%
|
20
76.9%
|
114
70.4%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | ||||||||
| American Indian or Alaska Native |
0
0%
|
1
4.8%
|
1
4.3%
|
1
3.8%
|
2
9.1%
|
1
4.8%
|
2
7.7%
|
8
4.9%
|
| Asian |
1
4.3%
|
0
0%
|
3
13%
|
1
3.8%
|
1
4.5%
|
0
0%
|
3
11.5%
|
9
5.6%
|
| Native Hawaiian or Other Pacific Islander |
1
4.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
0.6%
|
| Black or African American |
2
8.7%
|
8
38.1%
|
3
13%
|
9
34.6%
|
6
27.3%
|
3
14.3%
|
4
15.4%
|
35
21.6%
|
| White |
17
73.9%
|
12
57.1%
|
16
69.6%
|
15
57.7%
|
13
59.1%
|
16
76.2%
|
17
65.4%
|
106
65.4%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
2
8.7%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
4.8%
|
0
0%
|
3
1.9%
|
| serum phosphorus (mg/dL) [Mean (Standard Deviation) ] | ||||||||
| Mean (Standard Deviation) [mg/dL] |
7.55
(1.003)
|
7.92
(1.005)
|
7.32
(1.063)
|
7.76
(1.183)
|
7.73
(1.276)
|
7.61
(0.847)
|
7.87
(1.488)
|
7.68
(1.124)
|
Outcome Measures
| Title | Change in Serum Phosphate Levels |
|---|---|
| Description | Change in serum phosphate levels from the end of wash out (pre randomization value) to end of treatment |
| Time Frame | End of wash out (pre randomization value) to end of treatment (Day 29) |
Outcome Measure Data
| Analysis Population Description |
|---|
| two patients in the 30 mg bid group are not included in the analysis since they had no post randomization serum phosphorus measurements |
| Arm/Group Title | 1 mg Bid | 3 mg Bid | 10 mg Bid | 30 mg Bid | 3 mg od | 30 mg od | Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | 1 mg AZD1722 bid AZD1722: tenapanor, oral tablet | 3 mg AZD1722 bid AZD1722: tenapanor, oral tablet | 10 mg AZD1722 bid AZD1722: tenapanor, oral tablet | 30 mg AZD1722 bid AZD1722: tenapanor, oral tablet | 3 mg AZD1722 od AZD1722: tenapanor, oral tablet | 30 mg AZD1722 od AZD1722: tenapanor, oral tablet | Placebo (double dummy technique) Placebo: Placebo bid, double dummy technique |
| Measure Participants | 23 | 21 | 23 | 24 | 22 | 21 | 26 |
| Least Squares Mean (Standard Deviation) [mg/dL] |
-.47
(1.553)
|
-1.18
(1.391)
|
-1.7
(2.018)
|
-1.98
(2.007)
|
-.56
(1.763)
|
-1.11
(1.469)
|
-.54
(1.802)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 1 mg Bid, 3 mg Bid, 10 mg Bid, 30 mg Bid, 3 mg od, 30 mg od, Placebo |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.012 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Title | Change From Baseline in Calcium x Phosphorus Product |
|---|---|
| Description | Change from baseline (end of wash out) in calcium x phosphorus product |
| Time Frame | End of wash out (pre randomization value) to end of treatment (Day 29) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The number of patients analyzed are less than the randomized number since the data to accomplish the analysis was not available. |
| Arm/Group Title | 1 mg Bid | 3 mg Bid | 10 mg Bid | 30 mg Bid | 3 mg od | 30 mg od | Placebo |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | 1 mg AZD1722 bid AZD1722: tenapanor, oral tablet | 3 mg AZD1722 bid AZD1722: tenapanor, oral tablet | 10 mg AZD1722 bid AZD1722: tenapanor, oral tablet | 30 mg AZD1722 bid AZD1722: tenapanor, oral tablet | 3 mg AZD1722 od AZD1722: tenapanor, oral tablet | 30 mg AZD1722 od AZD1722: tenapanor, oral tablet | Placebo (double dummy technique) Placebo: Placebo bid, double dummy technique |
| Measure Participants | 22 | 19 | 20 | 23 | 21 | 20 | 24 |
| Mean (Standard Deviation) [mg/dL * mg/dL] |
-5.16
(9.75)
|
-12.02
(14.02)
|
-12.44
(15.94)
|
-16.6
(18.01)
|
-3.59
(18.59)
|
-11.02
(11.57)
|
-2.50
(13.67)
|
Adverse Events
| Time Frame | Adverse events were collected for a total of 5 weeks; 4-weeks of treatment and 1 treatment-free week | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||||
| Arm/Group Title | 1 mg Bid | 3 mg Bid | 10 mg Bid | 30 mg Bid | 3 mg od | 30 mg od | Placebo | |||||||
| Arm/Group Description | 1 mg AZD1722 bid AZD1722: tenapanor, oral tablet | 3 mg AZD1722 bid AZD1722: tenapanor, oral tablet | 10 mg AZD1722 bid AZD1722: tenapanor, oral tablet | 30 mg AZD1722 bid AZD1722: tenapanor, oral tablet | 3 mg AZD1722 od AZD1722: tenapanor, oral tablet | 30 mg AZD1722 od AZD1722: tenapanor, oral tablet | Placebo (double dummy technique) Placebo: Placebo bid, double dummy technique | |||||||
All Cause Mortality |
||||||||||||||
| 1 mg Bid | 3 mg Bid | 10 mg Bid | 30 mg Bid | 3 mg od | 30 mg od | Placebo | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/23 (4.3%) | 0/21 (0%) | 0/23 (0%) | 0/26 (0%) | 0/22 (0%) | 0/21 (0%) | 0/26 (0%) | |||||||
Serious Adverse Events |
||||||||||||||
| 1 mg Bid | 3 mg Bid | 10 mg Bid | 30 mg Bid | 3 mg od | 30 mg od | Placebo | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/23 (8.7%) | 2/21 (9.5%) | 3/23 (13%) | 2/26 (7.7%) | 1/22 (4.5%) | 0/21 (0%) | 4/26 (15.4%) | |||||||
| Blood and lymphatic system disorders | ||||||||||||||
| Anemia | 0/23 (0%) | 0 | 0/21 (0%) | 0 | 0/23 (0%) | 0 | 0/26 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/26 (3.8%) | 1 |
| Cardiac disorders | ||||||||||||||
| Chest pain | 1/23 (4.3%) | 1 | 0/21 (0%) | 0 | 0/23 (0%) | 0 | 1/26 (3.8%) | 1 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/26 (0%) | 0 |
| Cardiac failure | 1/23 (4.3%) | 1 | 0/21 (0%) | 0 | 0/23 (0%) | 0 | 0/26 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/26 (0%) | 0 |
| Acute Myocardial Infarction | 0/23 (0%) | 0 | 0/21 (0%) | 0 | 0/23 (0%) | 0 | 0/26 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/26 (3.8%) | 1 |
| Gastrointestinal disorders | ||||||||||||||
| Rectal prolapse | 0/23 (0%) | 0 | 0/21 (0%) | 0 | 0/23 (0%) | 0 | 1/26 (3.8%) | 1 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/26 (0%) | 0 |
| diarrhea | 0/23 (0%) | 0 | 0/21 (0%) | 0 | 0/23 (0%) | 0 | 0/26 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/26 (3.8%) | 1 |
| Infections and infestations | ||||||||||||||
| pneumonia | 0/23 (0%) | 0 | 1/21 (4.8%) | 1 | 0/23 (0%) | 0 | 0/26 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 1/26 (3.8%) | 1 |
| osteomyelitis | 0/23 (0%) | 0 | 0/21 (0%) | 0 | 1/23 (4.3%) | 1 | 0/26 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/26 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||||||
| Head injury | 0/23 (0%) | 0 | 1/21 (4.8%) | 1 | 0/23 (0%) | 0 | 0/26 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/26 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||||||||
| Fluid overload | 0/23 (0%) | 0 | 0/21 (0%) | 0 | 1/23 (4.3%) | 1 | 0/26 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/26 (0%) | 0 |
| Nervous system disorders | ||||||||||||||
| Syncope | 0/23 (0%) | 0 | 0/21 (0%) | 0 | 1/23 (4.3%) | 1 | 0/26 (0%) | 0 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/26 (0%) | 0 |
| Lacunar infarction | 0/23 (0%) | 0 | 0/21 (0%) | 0 | 0/23 (0%) | 0 | 0/26 (0%) | 0 | 1/22 (4.5%) | 1 | 0/21 (0%) | 0 | 0/26 (0%) | 0 |
| Vascular disorders | ||||||||||||||
| Deep vein thrombosis | 0/23 (0%) | 0 | 0/21 (0%) | 0 | 0/23 (0%) | 0 | 1/26 (3.8%) | 1 | 0/22 (0%) | 0 | 0/21 (0%) | 0 | 0/26 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||||||||
| 1 mg Bid | 3 mg Bid | 10 mg Bid | 30 mg Bid | 3 mg od | 30 mg od | Placebo | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 6/23 (26.1%) | 6/21 (28.6%) | 11/23 (47.8%) | 17/26 (65.4%) | 4/22 (18.2%) | 11/21 (52.4%) | 3/26 (11.5%) | |||||||
| Gastrointestinal disorders | ||||||||||||||
| Diarrhea | 6/23 (26.1%) | 6 | 6/21 (28.6%) | 6 | 11/23 (47.8%) | 11 | 17/26 (65.4%) | 17 | 4/22 (18.2%) | 4 | 11/21 (52.4%) | 11 | 3/26 (11.5%) | 3 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Chief Development Officer |
|---|---|
| Organization | Ardelyx |
| Phone | 6175134929 |
| drosenbaum@ardelyx.com |
Responsible Party:
Ardelyx
ClinicalTrials.gov Identifier:
NCT02081534
Other Study ID Numbers:
- D5613C00001
First Posted:
Mar 7, 2014
Last Update Posted:
Sep 14, 2020
Last Verified:
Aug 1, 2020