Study Assessing the Interaction of Pantoprazole With Cladribine in Subjects With Multiple Sclerosis

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: February 17, 2014
Last verified: January 2012
  Purpose

The purpose of the study is to assess the influence of pantoprazole on the pharmacokinetic profile of cladribine, especially any influence on the extent of absorption of cladribine since any pH-modifying drug may potentially affect the stability of cladribine and thereby its bioavailability


Condition Intervention Phase
Multiple Sclerosis
Drug: Cladribine
Drug: Cladribine and Pantoprazole
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: An Open-label, Cross Over Study, to Assess the Interactions of Pantoprazole (Proton Pump Inhibitor) With Oral Cladribine Administered in Subjects With Multiple Sclerosis.

Resource links provided by NLM:


Further study details as provided by Merck KGaA:

Primary Outcome Measures:
  • Maximum Plasma Concentration (Cmax) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Blood samples for pharmacokinetic analysis of cladribine were collected at pre-dose (within 30 minutes prior to dosing) and at 30 minutes, 1h, 3h, 6h, 8h, 12h, 16h and 24h post-dose during the confinement period and at 36h and 48h post-dose during ambulatory visits

  • 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) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Blood samples for pharmacokinetic analysis of cladribine were collected at pre-dose (within 30 minutes prior to dosing) and at 30 minutes, 1h, 3h, 6h, 8h, 12h, 16h and 24h post-dose during the confinement period and at 36h and 48h post-dose during ambulatory visits

  • Area under the plasma concentration-time curve from time zero to infinity (AUC0-∞) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Blood samples for pharmacokinetic analysis of cladribine were collected at pre-dose (within 30 minutes prior to dosing) and at 30 minutes, 1h, 3h, 6h, 8h, 12h, 16h and 24h post-dose during the confinement period and at 36h and 48h post-dose during ambulatory visits

  • Time to reach the maximum plasma concentration (tmax) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Blood samples for pharmacokinetic analysis of cladribine were collected at pre-dose (within 30 minutes prior to dosing) and at 30 minutes, 1h, 3h, 6h, 8h, 12h, 16h and 24h post-dose during the confinement period and at 36h and 48h post-dose during ambulatory visits

  • Apparent terminal half-life (t1/2) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Blood samples for pharmacokinetic analysis of cladribine were collected at pre-dose (within 30 minutes prior to dosing) and at 30 minutes, 1h, 3h, 6h, 8h, 12h, 16h and 24h post-dose during the confinement period and at 36h and 48h post-dose during ambulatory visits

  • Total body clearance from plasma following extravascular administration (CL/f) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Blood samples for pharmacokinetic analysis of cladribine were collected at pre-dose (within 30 minutes prior to dosing) and at 30 minutes, 1h, 3h, 6h, 8h, 12h, 16h and 24h post-dose during the confinement period and at 36h and 48h post-dose during ambulatory visits

  • Apparent volume of distribution during the terminal phase following extravascular administration (Vz/f) [ Time Frame: 24 hours ] [ Designated as safety issue: No ]
    Blood samples for pharmacokinetic analysis of cladribine were collected at pre-dose (within 30 minutes prior to dosing) and at 30 minutes, 1h, 3h, 6h, 8h, 12h, 16h and 24h post-dose during the confinement period and at 36h and 48h post-dose during ambulatory visits


Enrollment: 18
Study Start Date: January 2008
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cladribine alone/Cladribine plus Pantoprazole
Treatment sequence: Subjects received a single cladribine dose. After a wash out period of a minimum of 10 days and a maximum of 25 days, subjects received pantoprazole for 2 days. On day 2 of the pantoprazole administration, a single cladribine dose was administered 3 hours after the pantoprazole dose.
Drug: Cladribine
Cladribine 10 mg orally
Drug: Cladribine and Pantoprazole
Pantoprazole 40 mg per day orally, for 2 days ; Cladribine 10mg orally, 3 hours after Pantoprazole on the second day.
Experimental: Cladribine plus pantoprazole/Cladribine alone
Treatment sequence: Subjects received oral pantoprazole for 2 days. On day 2 of the pantoprazole administration, a single cladribine dose was administered 3 hours after the pantoprazole dose. After a wash out period of a minimum of 10 days and a maximum of 25 days, subjects received a single cladribine dose.
Drug: Cladribine
Cladribine 10 mg orally
Drug: Cladribine and Pantoprazole
Pantoprazole 40 mg per day orally, for 2 days ; Cladribine 10mg orally, 3 hours after Pantoprazole on the second day.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects with a Body Mass Index ≤ 28 and have a body weight > 60 kg and < 120 kg, at screening.
  • Able to understand informed consent and had given written, informed consent.
  • Had a diagnosis of clinically stable and definite multiple sclerosis (MS) by either McDonald or Poser criteria.
  • Expanded disability status scale (EDSS) score not to exceed 5.0.
  • Male or non-pregnant, non-breast feeding women aged 18 to 65 years, inclusive at the time that informed consent was obtained.
  • Female subjects had to lack childbearing potential defined as post menopausal for at least two years, were surgically or medically sterile or were sexually inactive; or they had to be willing to avoid pregnancy by using an adequate method of birth control (two barrier methods, or one barrier method with spermicide, or intrauterine device or use of the oral female contraceptive) for 28 days prior to, during and up to 90 days after the last administration of trial medication.

Exclusion Criteria:

  • Subjects presenting a severe or unstable disorder: poorly controlled diabetes or arterial hypertension, severe cardiac insufficiency, unstable ischemic heart disease, a significant pre-existing hematological disease, or any medical condition, which in the opinion of the investigator, would constitute a risk or a contraindication for the participation of the subject to the study or that could interfere with the study objectives, conduct or evaluation.
  • Subjects who were on MS treatment; and subjects who were on a non-stable symptomatic MS treatment (stable dose was defined as 3 weeks or longer prior to first study dose).
  • Clinically significant abnormal laboratory test results or electrocardiogram findings that in the opinion of the investigator could increase the safety risk to the subject.
  • Positive results from serology examination for Hepatitis B surface antigen (HbsAg) not due to vaccination, hepatitis B core antibody (HbcAb), Hepatitis C virus antibody (anti-HCV) or Human Immunodeficiency antibody (anti-HIV).
  • Signs and symptoms of Transmissible Spongiform Encephalopathy at screening, or family members who suffered from such.
  • Presence of chronic or recurrent infection or any acute infection within the last 2 weeks before first dosing in each study period.
  • Presence of gastrointestinal disease that, in the opinion of the investigator, could affect the pharmacokinetic outcome of the study.
  • Consumption of any concomitant medication that could directly influence gastric acidity (e.g. use of antacids, histamine receptor (H2) antagonists or other proton pump inhibitor) taken within 7 days of study day 1 and throughout the study period.
  • Intake of alcoholic beverages, caffeine and caffeine containing beverages, grapefruit, oranges, cranberries and juices of these three fruits or smoking in the 48 hours prior to first dose and 48 hours post dose (cladribine).
  • Exposure to any investigational drug or the use of any investigational device in the 12 weeks prior to first dose.
  • Intake of any medications that could directly influence gastrointestinal motility and absorption of cladribine (e.g., use of H2-antagonists, proton pump inhibitors) 7 days prior to cladribine administration.
  • Any immunomodulatory therapy (including but not limited to glatiramer acetate, interferons, or natalizumab) and treatment with oral or systemic corticosteroids or adrenocorticotropic hormone within 28 days of first dosing.
  • Any cytokine or anti-cytokine therapy, IV immunoglobulin administration or plasmapheresis was prohibited in the 3 months prior to first dosing.
  • Current history or presence of drug or alcohol abuse, confirmed by positive test results for drugs of abuse and/or alcohol or had a history of drug or alcohol abuse. Alcohol abuse was defined as: an average daily intake of more than 3 units or a weekly intake of more than 21 for males and 14 units for females where 1 unit equals 8-10g alcohol (1 unit equals 340 mL of beer, 115 mL of wine or 43 mL of spirits).
  • History or presence of hypertension or other significant cardiovascular abnormality, history of heart or kidney disease.
  • Current diagnosis or personal history of cancer.
  • Smoke 10 cigarettes or more per day or equivalent.
  • Loss or donation of more than 400 mL of blood in the 12 weeks prior to first dose.
  • Definite or suspected personal history or family history of adverse drug reaction or hypersensitivity to drugs with a similar chemical structure to cladribine or pantoprazole or with known hypersensitivity to cladribine or pantoprazole excipients.
  • Presence or history of any serious allergy (requiring hospitalization or prolonged systemic treatment).
  • Pregnant or nursing women. Treatment of pregnant and nursing women with cladribine in this study was prohibited.
  • Signs or symptoms of neurological disease other than MS that could explain the symptoms of the subject.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00938366

Sponsors and Collaborators
Merck KGaA
Merck Serono S.A., Geneva
Investigators
Study Director: Marianne Ekblom, PhD Merck Serono S.A., Geneva
  More Information

No publications provided

Responsible Party: Merck KGaA
ClinicalTrials.gov Identifier: NCT00938366     History of Changes
Other Study ID Numbers: 27967
Study First Received: July 9, 2009
Last Updated: February 17, 2014
Health Authority: Serbia: Agency for Drugs and Medicinal Devices
Germany: Federal Institute for Drugs and Medical Devices

Additional relevant MeSH terms:
Sclerosis
Multiple Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pantoprazole
Cladribine
Anti-Ulcer Agents
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Proton Pump Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014