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

NCT00938366 | Completed Phase 1 Results

• 1 other identifier: 27967
• Study Type: interventional
• Target: 18
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (2)

• Maximum Plasma Concentration (Cmax) of Cladribine

  The maximum or peak plasma concentration observed after the administration of cladribine.

  Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dose

• Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of Cladribine

  The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.

  Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dose

Secondary Outcomes (5)

• 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

  Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dose

• Time to Reach the Maximum Plasma Concentration (Tmax) of Cladribine

  Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dose

• Apparent Terminal Half-life (t1/2) of Cladribine

  Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dose

• Total Body Clearance From Plasma Following Extravascular Administration (CL/f) of Cladribine

  Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dose

• Percentage of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious AEs, AEs Leading to Death, and AEs Leading to Discontinuation

  Up to 1 year

Other Outcomes (1)

• Apparent Volume of Distribution During the Terminal Phase Following Extravascular Administration (Vz/f) of Cladribine

  Pre-dose (within 30 minutes prior to dosing) and at 0.5,1, 3, 6, 8, 12,16, 24, 36, 48 Hour post-dose

Study Arms (2)

Cladribine followed by Cladribine + Pantoprazole

EXPERIMENTAL

Subjects will receive a single dose of cladribine10 milligram (mg) orally on Day 1. After a wash out period of 10-25 days, subjects will receive pantoprazole 40 mg orally for 2 consecutive days. On Day 2 of the pantoprazole administration, a single dose of cladribine 10 mg will be administered orally 3 hours after the second pantoprazole dose.

Drug: Cladribine; Drug: Pantoprazole

Cladribine + pantoprazole followed by Cladribine

EXPERIMENTAL

Subjects will receive pantoprazole 40 mg orally for 2 consecutive days. On Day 2 of the pantoprazole administration, a single dose of cladribine 10 mg will be administered orally 3 hours after the second pantoprazole dose. After a wash out period of 10-25 days, subjects will receive a single dose of cladribine 10 mg orally.

Drug: Cladribine; Drug: Pantoprazole

Interventions

Cladribine DRUG

Subjects will receive two single doses of 10 mg cladribine orally in either first or second intervention period followed by a washout period of 10-25 days.

Cladribine + pantoprazole followed by Cladribine; Cladribine followed by Cladribine + Pantoprazole

Pantoprazole DRUG

Subjects will receive a pantoprazole 40 mg orally for 2 consecutive days either in first or second intervention period.

Cladribine + pantoprazole followed by Cladribine; Cladribine followed by Cladribine + Pantoprazole

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with a body mass index less than or equal to (\<=) 28 and have a body weight greater than (\>) 60 kilogram (kg) and less than (\<) 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 lacking childbearing potential defined as post-menopausal for at least two years, surgically or medically sterile or sexually inactive; or willing to avoid pregnancy by using an adequate method of birth control for 28 days prior to, during and up to 90 days after the last administration of trial medication

You may not qualify if:

• 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 (example: 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 (example, 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 8-10 gram alcohol (1 unit equals 340 milliliter \[mL\] 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

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead
• Merck Serono S.A., Geneva: collaborator

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Cladribine; Pantoprazole

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

2-Chloroadenosine; Adenosine; Purine Nucleosides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Deoxyadenosines; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Benzimidazoles

Results Point of Contact

• Title: Merck KGaA Communication Center
• Organization: Merck Serono, a division of Merck KGaA

service@merckgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible, PhD

  Merck Serono S.A. - Geneva, an affiliate of MerckKGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 9, 2009
• First Posted: July 13, 2009
• Study Start: January 1, 2008
• Primary Completion: January 1, 2009
• Study Completion: January 1, 2009
• Last Updated: April 14, 2016
• Results First Posted: October 20, 2015

Record last verified: 2016-03