Trial Outcomes & Findings for Head to Head Study Against Sevelamer Hydrochloride (NCT NCT00441545)
NCT ID: NCT00441545
Last Updated: 2021-06-11
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
182 participants
Primary outcome timeframe
4 weeks
Results posted on
2021-06-11
Participant Flow
Following Washout 1, eligible subjects with serum phosphorus levels greater than or equal to 6.0mg/dL (greater than or equal to 1.94mmol/L) and calcium levels greater than or equal to 8.4mg/dL (greater than or equal to 2.10mmol/L) were randomized in a 1:1 ratio to receive either Fosrenol or sevelamer hydrochloride (HCl) for 4 weeks.
The study consisted of the following phases: screening (1 week), washout 1 (2 weeks), treatment (4 weeks), Washout 2 (2 weeks), crossover treatment (4 weeks), and a 30-day follow-up
Participant milestones
| Measure |
Fosrenol First
Fosrenol (Lanthanum carbonate) dosing began at 2250mg/day, administered orally as one 750mg tablet taken three times per day with meals for 1 week. After receiving this dose for 1 week, subjects received the final dose of 3000mg/day, administered orally as one 1000mg tablet three times per day with meals. Subjects were to remain on the final Fosrenol dose of 3000mg/day for 3 weeks. After washout, patients then crossover to receive Sevelamer HCl for 4 weeks (see below).
|
Sevelamer HCl First
Sevelamer HCl dosing began at 4800mg/day, administered orally as two 800mg tablets taken three times per day with meals for 1 week. After receiving this dose for 1 week, subjects received the final dose of 6400mg/day, administered orally as three 800mg tablets taken two times per day with meals and two 800mg tablets taken once per day with the lighter meal (i.e., a total of eight 800mg tablets per day). Subjects were to remain on the final sevelamer HCl dose of 6400mg/day for 3 weeks. After washout, patients then crossover to receive Fosrenol for 4 weeks (see above).
|
|---|---|---|
|
First Intervention
STARTED
|
95
|
87
|
|
First Intervention
COMPLETED
|
77
|
75
|
|
First Intervention
NOT COMPLETED
|
18
|
12
|
|
Washout
STARTED
|
77
|
75
|
|
Washout
COMPLETED
|
77
|
75
|
|
Washout
NOT COMPLETED
|
0
|
0
|
|
Second Intervention
STARTED
|
77
|
75
|
|
Second Intervention
COMPLETED
|
65
|
68
|
|
Second Intervention
NOT COMPLETED
|
12
|
7
|
Reasons for withdrawal
| Measure |
Fosrenol First
Fosrenol (Lanthanum carbonate) dosing began at 2250mg/day, administered orally as one 750mg tablet taken three times per day with meals for 1 week. After receiving this dose for 1 week, subjects received the final dose of 3000mg/day, administered orally as one 1000mg tablet three times per day with meals. Subjects were to remain on the final Fosrenol dose of 3000mg/day for 3 weeks. After washout, patients then crossover to receive Sevelamer HCl for 4 weeks (see below).
|
Sevelamer HCl First
Sevelamer HCl dosing began at 4800mg/day, administered orally as two 800mg tablets taken three times per day with meals for 1 week. After receiving this dose for 1 week, subjects received the final dose of 6400mg/day, administered orally as three 800mg tablets taken two times per day with meals and two 800mg tablets taken once per day with the lighter meal (i.e., a total of eight 800mg tablets per day). Subjects were to remain on the final sevelamer HCl dose of 6400mg/day for 3 weeks. After washout, patients then crossover to receive Fosrenol for 4 weeks (see above).
|
|---|---|---|
|
First Intervention
Adverse Event
|
6
|
5
|
|
First Intervention
Protocol Violation
|
2
|
2
|
|
First Intervention
Withdrawal by Subject
|
3
|
3
|
|
First Intervention
Kidney transplant
|
1
|
1
|
|
First Intervention
Lack of Efficacy
|
2
|
0
|
|
First Intervention
Subject exceeded safety criteria
|
0
|
1
|
|
First Intervention
Subject met an exclusionary criteria
|
1
|
0
|
|
First Intervention
Extended hospitalization
|
1
|
0
|
|
First Intervention
Site error
|
1
|
0
|
|
First Intervention
Sponsor's request
|
1
|
0
|
|
Second Intervention
Adverse Event
|
5
|
2
|
|
Second Intervention
Protocol Violation
|
4
|
1
|
|
Second Intervention
Withdrawal by Subject
|
1
|
1
|
|
Second Intervention
Kidney Transplant
|
1
|
1
|
|
Second Intervention
Lack of Efficacy
|
0
|
1
|
|
Second Intervention
Subject exceeded safety criteria
|
1
|
0
|
|
Second Intervention
Subject moved
|
0
|
1
|
Baseline Characteristics
Head to Head Study Against Sevelamer Hydrochloride
Baseline characteristics by cohort
| Measure |
Entire Study Population
n=182 Participants
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
140 Participants
n=93 Participants
|
|
Age, Categorical
>=65 years
|
42 Participants
n=93 Participants
|
|
Age, Continuous
|
55.5 years
STANDARD_DEVIATION 13.10 • n=93 Participants
|
|
Sex: Female, Male
Female
|
80 Participants
n=93 Participants
|
|
Sex: Female, Male
Male
|
102 Participants
n=93 Participants
|
|
Region of Enrollment
United States
|
139 Participants
n=93 Participants
|
|
Region of Enrollment
Puerto Rico
|
1 Participants
n=93 Participants
|
|
Region of Enrollment
Germany
|
41 Participants
n=93 Participants
|
|
Region of Enrollment
United Kingdom
|
1 Participants
n=93 Participants
|
PRIMARY outcome
Timeframe: 4 weeksPopulation: ITT population defined as subjects who were randomized, received at least one dose of investigational product, and had at least one post-dose assessment of the primary efficacy variable.
Outcome measures
| Measure |
Fosrenol
n=165 Participants
Lanthanum carbonate
|
Sevelamer HCl
n=161 Participants
|
|---|---|---|
|
Change From Baseline in Serum Phosphorus Levels at 4 Weeks
|
-1.73 mg/dL
Standard Error 0.129
|
-1.44 mg/dL
Standard Error 0.132
|
SECONDARY outcome
Timeframe: 4 weeksPopulation: ITT
Outcome measures
| Measure |
Fosrenol
n=165 Participants
Lanthanum carbonate
|
Sevelamer HCl
n=161 Participants
|
|---|---|---|
|
Change From Baseline in Serum Calcium Levels at 4 Weeks
|
0.06 mg/dL
Standard Error 0.045
|
-0.06 mg/dL
Standard Error 0.046
|
SECONDARY outcome
Timeframe: Baseline and 4 weeksPopulation: ITT
Outcome measures
| Measure |
Fosrenol
n=165 Participants
Lanthanum carbonate
|
Sevelamer HCl
n=161 Participants
|
|---|---|---|
|
Levels of Intact Parathyroid Hormone (iPTH) at Baseline and 4 Weeks
Baseline
|
225.46 pg/mL
Standard Error 11.094
|
225.46 pg/mL
Standard Error 11.094
|
|
Levels of Intact Parathyroid Hormone (iPTH) at Baseline and 4 Weeks
Endpoint
|
296.48 pg/mL
Standard Error 17.412
|
291.18 pg/mL
Standard Error 16.181
|
SECONDARY outcome
Timeframe: 4 weeksKidney Disease Outcomes Quality Initiative (KDOQI) target for serum phosphorous is 3.5 - 5.5 mg/dL (1.13 - 1.77 mmol/L)
Outcome measures
| Measure |
Fosrenol
n=165 Participants
Lanthanum carbonate
|
Sevelamer HCl
n=161 Participants
|
|---|---|---|
|
Patients Achieving Kidney Disease Outcomes Quality Initiative (KDOQI) Target for Serum Phosphorous at 4 Weeks
|
42.7 Percentage of Participants
|
34.6 Percentage of Participants
|
Adverse Events
Fosrenol
Serious events: 18 serious events
Other events: 31 other events
Deaths: 0 deaths
Sevelamer HCl
Serious events: 20 serious events
Other events: 27 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Fosrenol
n=170 participants at risk
Fosrenol (Lanthanum carbonate) dosing began at 2250mg/day, administered orally as one 750mg tablet taken three times per day with meals for 1 week. After receiving this dose for 1 week, subjects received the final dose of 3000mg/day, administered orally as one 1000mg tablet three times per day with meals. Subjects were to remain on the final Fosrenol dose of 3000mg/day for 3 weeks. After washout, patients then crossover to receive Sevelamer HCl for 4 weeks (see below).
|
Sevelamer HCl
n=163 participants at risk
Sevelamer HCl dosing began at 4800mg/day, administered orally as two 800mg tablets taken three times per day with meals for 1 week. After receiving this dose for 1 week, subjects received the final dose of 6400mg/day, administered orally as three 800mg tablets taken two times per day with meals and two 800mg tablets taken once per day with the lighter meal (i.e., a total of eight 800mg tablets per day). Subjects were to remain on the final sevelamer HCl dose of 6400mg/day for 3 weeks. After washout, patients then crossover to receive Fosrenol for 4 weeks (see above).
|
|---|---|---|
|
Vascular disorders
Death
|
0.59%
1/170
|
0.00%
0/163
|
|
Cardiac disorders
Congestive heart failure
|
0.59%
1/170
|
1.2%
2/163
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/170
|
0.61%
1/163
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
0.59%
1/170
|
0.61%
1/163
|
|
Infections and infestations
Clostridium difficile colitis
|
0.00%
0/170
|
1.2%
2/163
|
|
Nervous system disorders
Presyncope
|
0.00%
0/170
|
0.61%
1/163
|
|
Infections and infestations
Foot infection
|
0.59%
1/170
|
0.61%
1/163
|
|
Cardiac disorders
Myocardial infarction
|
1.2%
2/170
|
1.2%
2/163
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/170
|
0.61%
1/163
|
|
General disorders
Weakness
|
0.00%
0/170
|
1.2%
2/163
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/170
|
0.61%
1/163
|
|
Cardiac disorders
Coronary atery disease
|
1.2%
2/170
|
1.2%
2/163
|
|
Infections and infestations
Osteomyelitis
|
1.2%
2/170
|
0.61%
1/163
|
|
Infections and infestations
Cellulitis
|
0.59%
1/170
|
0.61%
1/163
|
|
Infections and infestations
Pneumonia
|
1.8%
3/170
|
0.61%
1/163
|
|
Skin and subcutaneous tissue disorders
Extremity necrosis
|
0.00%
0/170
|
1.8%
3/163
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/170
|
0.61%
1/163
|
|
Gastrointestinal disorders
Abdominal pain
|
0.59%
1/170
|
0.61%
1/163
|
|
Infections and infestations
Cystitis
|
0.59%
1/170
|
0.61%
1/163
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
0.00%
0/170
|
0.61%
1/163
|
|
Infections and infestations
Septic phlebitis
|
0.59%
1/170
|
0.00%
0/163
|
|
Nervous system disorders
Stroke
|
0.59%
1/170
|
0.00%
0/163
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.59%
1/170
|
0.00%
0/163
|
|
Cardiac disorders
Unstable angina
|
0.59%
1/170
|
0.00%
0/163
|
|
Nervous system disorders
Cerebral vascular accident
|
1.8%
3/170
|
0.00%
0/163
|
|
Nervous system disorders
Pripheral neuropathy
|
0.59%
1/170
|
0.00%
0/163
|
|
General disorders
Chest pain
|
1.2%
2/170
|
0.00%
0/163
|
|
Vascular disorders
Hypotension
|
1.2%
2/170
|
0.00%
0/163
|
Other adverse events
| Measure |
Fosrenol
n=170 participants at risk
Fosrenol (Lanthanum carbonate) dosing began at 2250mg/day, administered orally as one 750mg tablet taken three times per day with meals for 1 week. After receiving this dose for 1 week, subjects received the final dose of 3000mg/day, administered orally as one 1000mg tablet three times per day with meals. Subjects were to remain on the final Fosrenol dose of 3000mg/day for 3 weeks. After washout, patients then crossover to receive Sevelamer HCl for 4 weeks (see below).
|
Sevelamer HCl
n=163 participants at risk
Sevelamer HCl dosing began at 4800mg/day, administered orally as two 800mg tablets taken three times per day with meals for 1 week. After receiving this dose for 1 week, subjects received the final dose of 6400mg/day, administered orally as three 800mg tablets taken two times per day with meals and two 800mg tablets taken once per day with the lighter meal (i.e., a total of eight 800mg tablets per day). Subjects were to remain on the final sevelamer HCl dose of 6400mg/day for 3 weeks. After washout, patients then crossover to receive Fosrenol for 4 weeks (see above).
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
8.8%
15/170
|
5.5%
9/163
|
|
Gastrointestinal disorders
Diarrhea
|
7.1%
12/170
|
7.4%
12/163
|
|
Gastrointestinal disorders
Vomiting
|
5.3%
9/170
|
3.7%
6/163
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
- Publication restrictions are in place
Restriction type: OTHER