Multiple SclerosisPhase 1NCT00938366
Drug-Drug Interaction of Cladribine and Pantoprazole in Multiple Sclerosis Subjects
A Phase 1 study testing Cladribine and Pantoprazole in people with Multiple Sclerosis, run by Merck KGaA, Darmstadt, Germany.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Cladribine and Pantoprazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- No sites listed yet
- Study dates
- Jan 2008to Jan 2009
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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
- 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
About this study
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
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
- Being tested
- Cladribine, Pantoprazole
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CladribineDrug
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.
PantoprazoleDrug
Subjects will receive a pantoprazole 40 mg orally for 2 consecutive days either in first or second intervention period.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Cladribine; Drug: Pantoprazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Plasma Concentration (Cmax) of Cladribine
The maximum or peak plasma concentration observed after the administration of cladribine.
Measured: 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.
Measured: 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
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).
Measured: 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
The tmax was defined as time taken by the drug cladribine to reach Cmax.
Measured: 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
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.
Measured: 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
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.
Measured: 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
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.
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2009 (estimated)
- Study startJan 2008
- Primary completionJan 2009
- Study completionJan 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck Serono S.A., Geneva
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, PhD, Study director, Merck Serono S.A. - Geneva, an affiliate of MerckKGaA, Darmstadt, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00938366
- Sponsor's protocol ID
- 27967
- Status last verified
- Mar 2016
- First submitted
- 9 Jul 2009
- Last updated
- 14 Apr 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00938366
- Acronym / sponsor ID
- 27967
- Conditions
- Multiple Sclerosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Collaborators
- Merck Serono S.A., Geneva
- Study start
- Jan 2008
- Primary completion
- Jan 2009 (actual)
- Study completion
- Jan 2009 (actual)
- First posted
- 13 Jul 2009 (estimated)
- Results
- Posted 20 Oct 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cladribine followed by Cladribine + Pantoprazole | Experimental | Drug: Cladribine, Drug: PantoprazoleSubjects 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. |
| Cladribine + pantoprazole followed by Cladribine | Experimental | Drug: Cladribine, Drug: PantoprazoleSubjects 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (22 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CladribineSubjects 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. | Drug | Cladribine + pantoprazole followed by Cladribine, Cladribine followed by Cladribine + Pantoprazole |
| PantoprazoleSubjects will receive a pantoprazole 40 mg orally for 2 consecutive days either in first or second intervention period. | Drug | Cladribine + pantoprazole followed by Cladribine, Cladribine followed by Cladribine + Pantoprazole |
Primary outcome
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.
5 secondary outcomes
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
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
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
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Responsible, PhD study director
Merck Serono S.A. - Geneva, an affiliate of MerckKGaA, Darmstadt, Germany
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cladribine and Pantoprazole in people with Multiple Sclerosis, run by Merck KGaA, Darmstadt, Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Oct 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2016.