Trial Outcomes & Findings for Drug-Drug Interaction of Cladribine and Pantoprazole in Multiple Sclerosis Subjects (NCT NCT00938366)
NCT ID: NCT00938366
Last Updated: 2016-04-14
Results Overview
The maximum or peak plasma concentration observed after the administration of cladribine.
COMPLETED
PHASE1
18 participants
Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dose
2016-04-14
Participant Flow
This was a crossover study.18 subjects were included and washout of 10 to 25 days separated each treatment period. Overall 17 subjects completed the trial.1 subject withdrew consent after completion of the first period (cladribine alone) and was excluded from Pharmacokinetic population.18 subjects were included in safety population.
Participant milestones
| Measure |
Cladribine Followed by Cladribine + Pantoprazole
Subjects received a single 10 milligram (mg) cladribine dose orally on Day 1 followed by a wash out period of 10-25 days. Subjects then received pantoprazole 40 mg orally for 2 consecutive days. A single 10 mg cladribine dose was administered orally after 3 hours of fasting post pantoprazole dose on second day. After administration of cladribine, subjects were required to fast for an additional 2 hours.
|
Cladribine + Pantoprazole Followed by Cladribine
Subjects received pantoprazole 40 mg orally for 2 consecutive days. A single 10 mg cladribine dose was administered orally after 3 hours of fasting post the pantoprazole dose on second day. After a wash out period of 10-25 days, subjects received a single 10 mg cladribine dose orally.
|
|---|---|---|
|
Overall Study
STARTED
|
9
|
9
|
|
Overall Study
COMPLETED
|
8
|
9
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Cladribine Followed by Cladribine + Pantoprazole
Subjects received a single 10 milligram (mg) cladribine dose orally on Day 1 followed by a wash out period of 10-25 days. Subjects then received pantoprazole 40 mg orally for 2 consecutive days. A single 10 mg cladribine dose was administered orally after 3 hours of fasting post pantoprazole dose on second day. After administration of cladribine, subjects were required to fast for an additional 2 hours.
|
Cladribine + Pantoprazole Followed by Cladribine
Subjects received pantoprazole 40 mg orally for 2 consecutive days. A single 10 mg cladribine dose was administered orally after 3 hours of fasting post the pantoprazole dose on second day. After a wash out period of 10-25 days, subjects received a single 10 mg cladribine dose orally.
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|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
Baseline Characteristics
Drug-Drug Interaction of Cladribine and Pantoprazole in Multiple Sclerosis Subjects
Baseline characteristics by cohort
| Measure |
Cladribine Followed by Cladribine + Pantoprazole
n=9 Participants
Subjects received a single 10 milligram (mg) cladribine dose orally on Day 1 followed by a wash out period of 10-25 days. Subjects then received pantoprazole 40 mg orally for 2 consecutive days. A single 10 mg cladribine dose was administered orally after 3 hours of fasting post the pantoprazole dose on second day. After administration of cladribine, subjects were required to fast for an additional 2 hours.
|
Cladribine + Pantoprazole Followed by Cladribine
n=9 Participants
Subjects received pantoprazole 40 mg orally for 2 consecutive days. A single 10 mg cladribine dose was administered orally after 3 hours of fasting post the pantoprazole dose on second day. After a wash out period of 10-25 days, subjects received a single 10 mg cladribine dose orally.
|
Total
n=18 Participants
Total of all reporting groups
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|---|---|---|---|
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Age, Continuous
|
44.56 years
STANDARD_DEVIATION 11.75 • n=5 Participants
|
46.89 years
STANDARD_DEVIATION 8.31 • n=7 Participants
|
45.72 years
STANDARD_DEVIATION 9.95 • n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dosePopulation: Pharmacokinetic (PK) analysis set included all the subjects who received cladribine alone and cladribine + pantoprazole according to the randomization and completed the full PK sampling.
The maximum or peak plasma concentration observed after the administration of cladribine.
Outcome measures
| Measure |
Cladribine
n=17 Participants
Subjects received two single doses of cladribine 10 mg orally in either first or second intervention period followed by a washout period of 10-25 days.
|
Cladribine + Pantoprazole
n=17 Participants
Subjects received pantoprazole 40 mg orally for 2 consecutive days. A single 10 mg cladribine dose was administered orally after 3 hours of fasting post the pantoprazole dose on second day in either first or second intervention period.
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|---|---|---|
|
Maximum Plasma Concentration (Cmax) of Cladribine
|
20.7 nanogram/milliliter
Geometric Coefficient of Variation 28.2
|
20.3 nanogram/milliliter
Geometric Coefficient of Variation 46.0
|
PRIMARY outcome
Timeframe: Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dosePopulation: The PK analysis set included all the subjects who received cladribine alone and cladribine + pantoprazole according to the randomization and completed the full PK sampling.
The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.
Outcome measures
| Measure |
Cladribine
n=17 Participants
Subjects received two single doses of cladribine 10 mg orally in either first or second intervention period followed by a washout period of 10-25 days.
|
Cladribine + Pantoprazole
n=17 Participants
Subjects received pantoprazole 40 mg orally for 2 consecutive days. A single 10 mg cladribine dose was administered orally after 3 hours of fasting post the pantoprazole dose on second day in either first or second intervention period.
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|---|---|---|
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Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Cladribine
|
74.6 hour*nanogram/milliliter
Geometric Coefficient of Variation 27.7
|
75.0 hour*nanogram/milliliter
Geometric Coefficient of Variation 34.8
|
SECONDARY outcome
Timeframe: Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dosePopulation: The PK analysis set included all the subjects who received cladribine alone and cladribine + pantoprazole according to the randomization and completed the full PK sampling.
The AUC (0-t) was defined as the area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-t).
Outcome measures
| Measure |
Cladribine
n=17 Participants
Subjects received two single doses of cladribine 10 mg orally in either first or second intervention period followed by a washout period of 10-25 days.
|
Cladribine + Pantoprazole
n=17 Participants
Subjects received pantoprazole 40 mg orally for 2 consecutive days. A single 10 mg cladribine dose was administered orally after 3 hours of fasting post the pantoprazole dose on second day in either first or second intervention period.
|
|---|---|---|
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Area Under the Plasma Concentration-time Curve From Time Zero to the Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of Cladribine
|
71.5 hour*nanogram/milliliter
Geometric Coefficient of Variation 28.0
|
71.3 hour*nanogram/milliliter
Geometric Coefficient of Variation 36.6
|
SECONDARY outcome
Timeframe: Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dosePopulation: The PK analysis set included all the subjects who received cladribine alone and cladribine + pantoprazole according to the randomization and completed the full PK sampling.
The tmax was defined as time taken by the drug cladribine to reach Cmax.
Outcome measures
| Measure |
Cladribine
n=17 Participants
Subjects received two single doses of cladribine 10 mg orally in either first or second intervention period followed by a washout period of 10-25 days.
|
Cladribine + Pantoprazole
n=17 Participants
Subjects received pantoprazole 40 mg orally for 2 consecutive days. A single 10 mg cladribine dose was administered orally after 3 hours of fasting post the pantoprazole dose on second day in either first or second intervention period.
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|---|---|---|
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Time to Reach the Maximum Plasma Concentration (Tmax) of Cladribine
|
0.5 hour
Interval 0.5 to 1.0
|
0.6 hour
Interval 0.5 to 1.0
|
SECONDARY outcome
Timeframe: Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dosePopulation: The PK analysis set included all the subjects who received cladribine alone and cladribine + pantoprazole according to the randomization and completed the full PK sampling.
The apparent terminal half-life was defined as the time required for the plasma concentration of drug cladribine to decrease 50 percent (%) in the final stage of its elimination.
Outcome measures
| Measure |
Cladribine
n=17 Participants
Subjects received two single doses of cladribine 10 mg orally in either first or second intervention period followed by a washout period of 10-25 days.
|
Cladribine + Pantoprazole
n=17 Participants
Subjects received pantoprazole 40 mg orally for 2 consecutive days. A single 10 mg cladribine dose was administered orally after 3 hours of fasting post the pantoprazole dose on second day in either first or second intervention period.
|
|---|---|---|
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Apparent Terminal Half-life (t1/2) of Cladribine
|
14.0 hour
Geometric Coefficient of Variation 18.2
|
14.9 hour
Geometric Coefficient of Variation 23.8
|
SECONDARY outcome
Timeframe: Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dosePopulation: The PK analysis set included all the subjects who received cladribine alone and cladribine + pantoprazole according to the randomization and completed the full PK sampling.
Clearance of a drug was a measure of the rate at which cladribine is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose was influenced by the fraction of the dose absorbed.
Outcome measures
| Measure |
Cladribine
n=17 Participants
Subjects received two single doses of cladribine 10 mg orally in either first or second intervention period followed by a washout period of 10-25 days.
|
Cladribine + Pantoprazole
n=17 Participants
Subjects received pantoprazole 40 mg orally for 2 consecutive days. A single 10 mg cladribine dose was administered orally after 3 hours of fasting post the pantoprazole dose on second day in either first or second intervention period.
|
|---|---|---|
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Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of Cladribine
|
134.0 liter/hour
Geometric Coefficient of Variation 27.7
|
133.3 liter/hour
Geometric Coefficient of Variation 34.8
|
SECONDARY outcome
Timeframe: Up to 1 yearPopulation: Safety analysis set included all the randomized subjects who received treatment with at least one dose of either cladribine or pantoprazole during the study period.
An AE was any untoward medical occurrence in a subject who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 1 year, that were absent before treatment or that worsened relative to pre treatment state. AEs Leading to Death and AEs Leading to Discontinuation were also presented in the outcome measure.
Outcome measures
| Measure |
Cladribine
n=18 Participants
Subjects received two single doses of cladribine 10 mg orally in either first or second intervention period followed by a washout period of 10-25 days.
|
Cladribine + Pantoprazole
n=17 Participants
Subjects received pantoprazole 40 mg orally for 2 consecutive days. A single 10 mg cladribine dose was administered orally after 3 hours of fasting post the pantoprazole dose on second day in either first or second intervention period.
|
|---|---|---|
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Percentage of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious AEs, AEs Leading to Death, and AEs Leading to Discontinuation
TEAEs
|
11.1 percentage of subjects
|
0.0 percentage of subjects
|
|
Percentage of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious AEs, AEs Leading to Death, and AEs Leading to Discontinuation
SAEs
|
0.0 percentage of subjects
|
0.0 percentage of subjects
|
|
Percentage of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious AEs, AEs Leading to Death, and AEs Leading to Discontinuation
AEs Leading to Death
|
0.0 percentage of subjects
|
0.0 percentage of subjects
|
|
Percentage of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious AEs, AEs Leading to Death, and AEs Leading to Discontinuation
AEs Leading to Discontinuation
|
0.0 percentage of subjects
|
0.0 percentage of subjects
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dosePopulation: The PK analysis set included all the subjects who received cladribine alone and cladribine + pantoprazole according to the randomization and completed the full PK sampling.
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
Outcome measures
| Measure |
Cladribine
n=17 Participants
Subjects received two single doses of cladribine 10 mg orally in either first or second intervention period followed by a washout period of 10-25 days.
|
Cladribine + Pantoprazole
n=17 Participants
Subjects received pantoprazole 40 mg orally for 2 consecutive days. A single 10 mg cladribine dose was administered orally after 3 hours of fasting post the pantoprazole dose on second day in either first or second intervention period.
|
|---|---|---|
|
Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/f) of Cladribine
|
2709 liter
Geometric Coefficient of Variation 32
|
2875 liter
Geometric Coefficient of Variation 46
|
Adverse Events
Cladribine
Cladribine + Pantoprazole
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Cladribine
n=18 participants at risk
Subjects received two single doses of cladribine 10 mg orally in either first or second intervention period followed by a washout period of 10-25 days.
|
Cladribine + Pantoprazole
n=17 participants at risk
Subjects received pantoprazole 40 mg orally for 2 consecutive days. A single 10 mg cladribine dose was administered orally after 3 hours of fasting post the pantoprazole dose on second day in either first or second intervention period.
|
|---|---|---|
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Gastrointestinal disorders
Abdominal distension
|
5.6%
1/18 • Up to 1 year
|
0.00%
0/17 • Up to 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
5.6%
1/18 • Up to 1 year
|
0.00%
0/17 • Up to 1 year
|
Additional Information
Merck KGaA Communication Center
Merck Serono, a division of Merck KGaA
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: OTHER