An Open-label, Cross Over Study, to Assess the Interactions of Pantoprazole (Proton Pump Inhibitor) With Oral Cladribine Administered in Subjects With Multiple Sclerosis
Overview
- Phase
- Phase 1
- Intervention
- Cladribine
- Conditions
- Multiple Sclerosis
- Sponsor
- Merck KGaA, Darmstadt, Germany
- Enrollment
- 18
- Primary Endpoint
- Maximum Plasma Concentration (Cmax) of Cladribine
- Status
- Completed
- Last Updated
- 10 years ago
Overview
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
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
- •Other protocol defined inclusion criteria could apply.
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 (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
Arms & Interventions
Cladribine followed by Cladribine + Pantoprazole
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.
Intervention: Cladribine
Cladribine followed by Cladribine + Pantoprazole
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.
Intervention: Pantoprazole
Cladribine + pantoprazole followed by Cladribine
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.
Intervention: Cladribine
Cladribine + pantoprazole followed by Cladribine
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.
Intervention: Pantoprazole
Outcomes
Primary Outcomes
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
The maximum or peak plasma concentration observed after the administration of cladribine.
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
The AUC(0-inf) was estimated by determining the total area under the curve of the concentration versus time curve extrapolated to infinity.
Secondary Outcomes
- 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)
- 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)
- 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)