Drug-Drug Interaction of Cladribine and Pantoprazole in Multiple Sclerosis Subjects

This study has been completed.
Sponsor:
Collaborator:
Merck Serono S.A., Geneva
Information provided by (Responsible Party):
Merck KGaA
ClinicalTrials.gov Identifier:
NCT00938366
First received: July 9, 2009
Last updated: March 15, 2016
Last verified: March 2016
Results First Received: September 21, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Pharmacokinetics Study;   Intervention Model: Crossover Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Multiple Sclerosis
Interventions: Drug: Cladribine
Drug: Pantoprazole

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
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.

Participant Flow:   Overall Study
    Cladribine Followed by Cladribine + Pantoprazole     Cladribine + Pantoprazole Followed by Cladribine  
STARTED     9     9  
COMPLETED     8     9  
NOT COMPLETED     1     0  
Withdrawal by Subject                 1                 0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Baseline analysis population included all randomized subjects.

Reporting Groups
  Description
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 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 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 Total of all reporting groups

Baseline Measures
    Cladribine Followed by Cladribine + Pantoprazole     Cladribine + Pantoprazole Followed by Cladribine     Total  
Number of Participants  
[units: participants]
  9     9     18  
Age  
[units: years]
Mean (Standard Deviation)
  44.56  (11.75)     46.89  (8.31)     45.72  (9.95)  
Gender  
[units: subjects]
     
Female     4     4     8  
Male     5     5     10  



  Outcome Measures
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1.  Primary:   Maximum Plasma Concentration (Cmax) of Cladribine   [ Time Frame: Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dose ]

2.  Primary:   Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Cladribine   [ Time Frame: Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dose ]

3.  Secondary:   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   [ Time Frame: Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dose ]

4.  Secondary:   Time to Reach the Maximum Plasma Concentration (Tmax) of Cladribine   [ Time Frame: Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dose ]

5.  Secondary:   Apparent Terminal Half-life (t1/2) of Cladribine   [ Time Frame: Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dose ]

6.  Secondary:   Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of Cladribine   [ Time Frame: Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dose ]

7.  Secondary:   Percentage of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious AEs, AEs Leading to Death, and AEs Leading to Discontinuation   [ Time Frame: Up to 1 year ]

8.  Other Pre-specified:   Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/f) of Cladribine   [ Time Frame: Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dose ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked 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 less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked 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: Merck KGaA Communication Center
Organization: Merck Serono, a division of Merck KGaA
phone: +49-6151-72-5200
e-mail: service@merckgroup.com



Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT00938366     History of Changes
Other Study ID Numbers: 27967
Study First Received: July 9, 2009
Results First Received: September 21, 2015
Last Updated: March 15, 2016
Health Authority: Serbia: Agency for Drugs and Medicinal Devices
Germany: Federal Institute for Drugs and Medical Devices