Trial Outcomes & Findings for The Pharmacokinetics of Rocaltrol When Administered Alone or in Combination With Fosrenol or Renvela in Healthy Volunteers (NCT NCT00925704)
NCT ID: NCT00925704
Last Updated: 2021-06-15
Results Overview
This shows the effect that lanthanum carbonate or sevelamer carbonate has on the pharmacokinetics of oral calcitriol. Exogenous calcitriol was the difference between total calcitriol value and the baseline exogenous calcitriol value at each sampling timepoint.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
41 participants
Primary outcome timeframe
pre-dose, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, and 48 hours post calcitriol dose
Results posted on
2021-06-15
Participant Flow
Patients were randomly assigned to 1 of 6 treatment sequences which consisted of 3 treatment periods separated by a washout of 7 days. In each of the treatment periods subjects received lanthanum carbonate + calcitriol, sevelamer carbonate + calcitriol or calcitriol alone.
Participant milestones
| Measure |
Sequence 1
Calcitriol (1.0 microgram) single dose at lunch for one day in first intervention, washout, Lanthanum carbonate (1000 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch) for one day in second intervention, washout, Sevelamer carbonate (2400 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch) for one day in third intervention
|
Sequence 2
Lanthanum carbonate (1000 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch) for one day in first intervention, washout, Calcitriol (1.0 microgram) single dose at lunch for one day in second intervention, washout, Sevelamer carbonate (2400 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch) for one day in third intervention
|
Sequence 3
Lanthanum carbonate (1000 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch) for one day in first intervention, washout, Sevelamer carbonate (2400 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch) for one day in second intervention, washout, Calcitriol (1.0 microgram) single dose at lunch for one day in third intervention
|
Sequence 4
Sevelamer carbonate (2400 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch) for one day in first intervention, washout, Calcitriol (1.0 microgram) single dose at lunch for one day in second intervention, washout, Lanthanum carbonate (1000 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch)for one day in third intervention
|
Sequence 5
Sevelamer carbonate (2400 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch) for one day in first intervention, washout, Lanthanum carbonate (1000 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch) for one day in second intervention, washout, Calcitriol (1.0 microgram) single dose at lunch for one day in third intervention
|
Sequence 6
Calcitriol (1.0 microgram) single dose at lunch for one day in first intervention, washout, Sevelamer carbonate (2400 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch) for one day in second intervention, washout, Lanthanum carbonate (1000 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch)for one day in third intervention
|
|---|---|---|---|---|---|---|
|
First Intervention
STARTED
|
6
|
7
|
7
|
7
|
7
|
7
|
|
First Intervention
COMPLETED
|
6
|
7
|
7
|
6
|
6
|
7
|
|
First Intervention
NOT COMPLETED
|
0
|
0
|
0
|
1
|
1
|
0
|
|
Washout
STARTED
|
5
|
7
|
7
|
6
|
5
|
7
|
|
Washout
COMPLETED
|
5
|
7
|
7
|
6
|
5
|
7
|
|
Washout
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
0
|
|
Second Intervention
STARTED
|
6
|
7
|
7
|
6
|
6
|
7
|
|
Second Intervention
COMPLETED
|
5
|
7
|
7
|
6
|
5
|
7
|
|
Second Intervention
NOT COMPLETED
|
1
|
0
|
0
|
0
|
1
|
0
|
|
Third Intervention
STARTED
|
5
|
7
|
7
|
6
|
5
|
7
|
|
Third Intervention
COMPLETED
|
5
|
7
|
7
|
6
|
5
|
6
|
|
Third Intervention
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
1
|
Reasons for withdrawal
| Measure |
Sequence 1
Calcitriol (1.0 microgram) single dose at lunch for one day in first intervention, washout, Lanthanum carbonate (1000 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch) for one day in second intervention, washout, Sevelamer carbonate (2400 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch) for one day in third intervention
|
Sequence 2
Lanthanum carbonate (1000 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch) for one day in first intervention, washout, Calcitriol (1.0 microgram) single dose at lunch for one day in second intervention, washout, Sevelamer carbonate (2400 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch) for one day in third intervention
|
Sequence 3
Lanthanum carbonate (1000 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch) for one day in first intervention, washout, Sevelamer carbonate (2400 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch) for one day in second intervention, washout, Calcitriol (1.0 microgram) single dose at lunch for one day in third intervention
|
Sequence 4
Sevelamer carbonate (2400 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch) for one day in first intervention, washout, Calcitriol (1.0 microgram) single dose at lunch for one day in second intervention, washout, Lanthanum carbonate (1000 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch)for one day in third intervention
|
Sequence 5
Sevelamer carbonate (2400 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch) for one day in first intervention, washout, Lanthanum carbonate (1000 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch) for one day in second intervention, washout, Calcitriol (1.0 microgram) single dose at lunch for one day in third intervention
|
Sequence 6
Calcitriol (1.0 microgram) single dose at lunch for one day in first intervention, washout, Sevelamer carbonate (2400 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch) for one day in second intervention, washout, Lanthanum carbonate (1000 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch)for one day in third intervention
|
|---|---|---|---|---|---|---|
|
First Intervention
Withdrew consent
|
0
|
0
|
0
|
1
|
1
|
0
|
|
Second Intervention
Withdrawal by Subject
|
1
|
0
|
0
|
0
|
1
|
0
|
|
Third Intervention
Withdrew consent
|
0
|
0
|
0
|
0
|
0
|
1
|
Baseline Characteristics
The Pharmacokinetics of Rocaltrol When Administered Alone or in Combination With Fosrenol or Renvela in Healthy Volunteers
Baseline characteristics by cohort
| Measure |
Sequence 1
n=6 Participants
Calcitriol (1.0 microgram) single dose at lunch for one day in first intervention, washout, Lanthanum carbonate (1000 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch) for one day in second intervention, washout, Sevelamer carbonate (2400 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch) for one day in third intervention
|
Sequence 2
n=7 Participants
Lanthanum carbonate (1000 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch) for one day in first intervention, washout, Calcitriol (1.0 microgram) single dose at lunch for one day in second intervention, washout, Sevelamer carbonate (2400 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch) for one day in third intervention
|
Sequence 3
n=7 Participants
Lanthanum carbonate (1000 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch) for one day in first intervention, washout, Sevelamer carbonate (2400 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch) for one day in second intervention, washout, Calcitriol (1.0 microgram) single dose at lunch for one day in third intervention
|
Sequence 4
n=7 Participants
Sevelamer carbonate (2400 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch) for one day in first intervention, washout, Calcitriol (1.0 microgram) single dose at lunch for one day in second intervention, washout, Lanthanum carbonate (1000 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch)for one day in third intervention
|
Sequence 5
n=7 Participants
Sevelamer carbonate (2400 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch) for one day in first intervention, washout, Lanthanum carbonate (1000 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch) for one day in second intervention, washout, Calcitriol (1.0 microgram) single dose at lunch for one day in third intervention
|
Sequence 6
n=7 Participants
Calcitriol (1.0 microgram) single dose at lunch for one day in first intervention, washout, Sevelamer carbonate (2400 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch) for one day in second intervention, washout, Lanthanum carbonate (1000 mg three times daily with meals) + Calcitriol (1 microgram single dose at lunch)for one day in third intervention
|
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
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
6 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
7 Participants
n=10 Participants
|
41 Participants
n=115 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Age, Continuous
|
27.7 years
STANDARD_DEVIATION 8.94 • n=5 Participants
|
30.0 years
STANDARD_DEVIATION 6.24 • n=7 Participants
|
30.9 years
STANDARD_DEVIATION 5.52 • n=5 Participants
|
28.4 years
STANDARD_DEVIATION 7.28 • n=4 Participants
|
31.0 years
STANDARD_DEVIATION 8.52 • n=21 Participants
|
30.4 years
STANDARD_DEVIATION 10.41 • n=10 Participants
|
29.8 years
STANDARD_DEVIATION 7.55 • n=115 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
3 Participants
n=10 Participants
|
19 Participants
n=115 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
4 Participants
n=10 Participants
|
22 Participants
n=115 Participants
|
|
Region of Enrollment
United States
|
6 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
7 Participants
n=21 Participants
|
7 Participants
n=10 Participants
|
41 Participants
n=115 Participants
|
PRIMARY outcome
Timeframe: pre-dose, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, and 48 hours post calcitriol dosePopulation: Pharmacokinetic set (PK) consists of subjects who received at least 1 dose of investigational product, had evaluable serum concentration-time profiles for calcitriol through 48 hours post-dosing on Day 1 of any treatment period and did not vomit between dosing and 10 hours post-dose on Day 1 of that treatment period.
This shows the effect that lanthanum carbonate or sevelamer carbonate has on the pharmacokinetics of oral calcitriol. Exogenous calcitriol was the difference between total calcitriol value and the baseline exogenous calcitriol value at each sampling timepoint.
Outcome measures
| Measure |
Calcitriol (Lanthanum Carbonate)
n=41 Participants
This group is the least squares mean of AUC 0-48 Lanthanum carbonate + Calcitriol minus least squares mean of AUC 0-48 Calcitriol alone.
|
Calcitriol (Sevelamer Carbonate)
n=41 Participants
This group is the least squares mean of AUC 0-48 Sevelamer carbonate + Calcitriol minus least squares mean of AUC 0-48 Calcitriol alone.
|
|---|---|---|
|
Area Under the Serum Concentration-time Curve (AUC 0-48) for Exogenous Calcitriol
|
111 pg*h/ml
Interval -48.9 to 270.0
|
-181 pg*h/ml
Interval -338.0 to -24.0
|
SECONDARY outcome
Timeframe: pre-dose, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, and 48 hours post calcitriol dosePopulation: PK set
This shows the effect that lanthanum carbonate or sevelamer carbonate has on the pharmacokinetics of oral calcitriol. Exogenous calcitriol was the difference between total calcitriol value and the baseline exogenous calcitriol value at each sampling timepoint.
Outcome measures
| Measure |
Calcitriol (Lanthanum Carbonate)
n=41 Participants
This group is the least squares mean of AUC 0-48 Lanthanum carbonate + Calcitriol minus least squares mean of AUC 0-48 Calcitriol alone.
|
Calcitriol (Sevelamer Carbonate)
n=41 Participants
This group is the least squares mean of AUC 0-48 Sevelamer carbonate + Calcitriol minus least squares mean of AUC 0-48 Calcitriol alone.
|
|---|---|---|
|
Maximum Plasma Concentration (Cmax) for Exogenous Calcitriol
|
-2.74 pg/ml
Interval -8.12 to 2.63
|
-9.62 pg/ml
Interval -14.9 to -4.34
|
SECONDARY outcome
Timeframe: pre-dose, 1, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, and 48 hours post calcitriol dosePopulation: PK set
This shows the effect that lanthanum carbonate or sevelamer carbonate has on the pharmacokinetics of oral calcitriol. Exogenous calcitriol was the difference between total calcitriol value and the baseline exogenous calcitriol value at each sampling timepoint.
Outcome measures
| Measure |
Calcitriol (Lanthanum Carbonate)
n=41 Participants
This group is the least squares mean of AUC 0-48 Lanthanum carbonate + Calcitriol minus least squares mean of AUC 0-48 Calcitriol alone.
|
Calcitriol (Sevelamer Carbonate)
n=41 Participants
This group is the least squares mean of AUC 0-48 Sevelamer carbonate + Calcitriol minus least squares mean of AUC 0-48 Calcitriol alone.
|
|---|---|---|
|
Time of Maximum Plasma Concentration (Tmax) for Exogenous Calcitriol
|
1.27 hours
Interval 0.0 to 2.48
|
0.500 hours
Interval 0.0 to 1.46
|
Adverse Events
Lanthanum Carbonate + Calcitriol
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Sevelamer Carbonate + Calcitriol
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Calcitriol Alone
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Lanthanum Carbonate + Calcitriol
n=38 participants at risk
Lanthanum carbonate (1000 mg three times daily with meals for one day) + Calcitriol (1 microgram single dose at lunch)
|
Sevelamer Carbonate + Calcitriol
n=40 participants at risk
Sevelamer carbonate (2400 mg three times daily with meals for one day) + Calcitriol (1 microgram single dose at lunch)
|
Calcitriol Alone
n=38 participants at risk
Calcitriol (1.0 microgram) single dose at lunch
|
|---|---|---|---|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
5.3%
2/38 • Number of events 2
Safety Set consisted of all enrolled subjects who received at least 1 dose of investigational product and had at least 1 post-dose safety assessment.
|
0.00%
0/40
Safety Set consisted of all enrolled subjects who received at least 1 dose of investigational product and had at least 1 post-dose safety assessment.
|
0.00%
0/38
Safety Set consisted of all enrolled subjects who received at least 1 dose of investigational product and had at least 1 post-dose safety assessment.
|
|
Nervous system disorders
Headache
|
5.3%
2/38 • Number of events 2
Safety Set consisted of all enrolled subjects who received at least 1 dose of investigational product and had at least 1 post-dose safety assessment.
|
5.0%
2/40 • Number of events 2
Safety Set consisted of all enrolled subjects who received at least 1 dose of investigational product and had at least 1 post-dose safety assessment.
|
2.6%
1/38 • Number of events 1
Safety Set consisted of all enrolled subjects who received at least 1 dose of investigational product and had at least 1 post-dose safety assessment.
|
|
Psychiatric disorders
Anxiety
|
5.3%
2/38 • Number of events 2
Safety Set consisted of all enrolled subjects who received at least 1 dose of investigational product and had at least 1 post-dose safety assessment.
|
0.00%
0/40
Safety Set consisted of all enrolled subjects who received at least 1 dose of investigational product and had at least 1 post-dose safety assessment.
|
0.00%
0/38
Safety Set consisted of all enrolled subjects who received at least 1 dose of investigational product and had at least 1 post-dose safety assessment.
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/38
Safety Set consisted of all enrolled subjects who received at least 1 dose of investigational product and had at least 1 post-dose safety assessment.
|
0.00%
0/40
Safety Set consisted of all enrolled subjects who received at least 1 dose of investigational product and had at least 1 post-dose safety assessment.
|
5.3%
2/38 • Number of events 2
Safety Set consisted of all enrolled subjects who received at least 1 dose of investigational product and had at least 1 post-dose safety assessment.
|
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