HealthyPhase 1NCT02495831
Drug Interaction Study of Safinamide and a BCRP Substrate, Diclofenac, Concomitantly Administered to Healthy Volunteers
A Phase 1 study testing Diclofenac sodium and Diclofenac sodium and safinamide in people with Healthy, run by Zambon SpA at 1 site in Switzerland.
Trial summary
To evaluate if a single dose of safinamide 200 mg has an effect on the pharmacokinetics of diclofenamic acid, concomitantly administered as a single 50 mg diclofenac sodium dose, with respect to 50 mg diclofenac sodium administered alone. Read more about this study
- Who is it for?
- Ages 22 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Diclofenac sodium and Diclofenac sodium and safinamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteSwitzerland
- Study dates
- May 2015to May 2015
- 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 22 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Signed written informed consent before inclusion in the study
- Males and females, 25-55 years old
- Body Mass Index (BMI): 18.5-30 kg/m2
- Systolic blood pressure 100-139 mmHg, diastolic blood pressure 50-89 mmHg, heart rate 50-90 bpm
- Ability to comprehend the full nature and purpose of the study
- Females of child-bearing potential must use at least one of the following :
- A non-hormonal intrauterine device or female condom with spermicide or contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap with spermicide for at least 2 months before the screening visit A male sexual partner who agreed to use a male condom with spermicide A sterile sexual partner Female participants of non-child-bearing potential or in post-menopausal status for at least 1 year were admitted.
Who cannot join
- Contraindications to MAO-B inhibitors, antiepileptic drugs, or to any NSAIDs
- Clinically significant abnormalities in ECG
- Clinically significant abnormal physical findings
- Clinically significant abnormal laboratory values
- Hypersensitivity or history of anaphylaxis to drugs or allergic reactions in general
- Significant history of renal, hepatic, gastrointestinal, cardiovascular, respiratory, skin, haematological, endocrine or neurological diseases
Show all 14Show fewer
- Medications, including over the counter medications and herbal remedies, NSAID or anticoagulant use for 2 weeks before and during the entire study; morphine or other similar opioids, SSRIs, SNRIs, tri- or tetracyclic antidepressant, tramadol, pethidine, dextromethorphan, MAO inhibitors, meperidine derivatives and antiepileptic drugs, medicinal products that are BCRP substrates, any known enzyme inhibiting or inducing agent within 4 weeks preceding the screening visit.
- Participation in the evaluation of any investigational product for 3 months before the study.
- Blood donations for 3 months before the study
- History of drug, alcohol, caffeine or tobacco abuse
- Positive drug test at screening or day -1
- Positive alcohol breath test at day -1
- Abnormal diets or substantial changes in eating habits in the 4 weeks before the study; vegetarians
- Positive or missing pregnancy test at screening or day -1, pregnant or lactating women
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
Cross Research SA, Phase I Unit
Arzo, Canton Ticino, 6864
About this study
To evaluate if a single dose of safinamide 200 mg has an effect on the pharmacokinetics of diclofenamic acid, concomitantly administered as a single 50 mg diclofenac sodium dose, with respect to 50 mg diclofenac sodium administered alone.
Read the detailed description
According to Xadago™ SmPC, safinamide may transiently inhibit BCRP, therefore a time interval of 5 h should be kept between dosing of safinamide and medicinal products that are BCRP substrates with a Tmax ≤2 h (e.g. diclofenac, pitavastatin, pravastatin, ciprofloxacin, methotrexate, topotecan or glyburide).
Following a specific request of EMA CHMP, the present interaction study in healthy male and female volunteers was conducted to determine if co-administration of safinamide with a BCRP substrate alters plasma exposure of the BCRP substrate in vivo.
Diclofenac was chosen among the other BCRP substrates considering its large use in the general population. Diclofenac in fact is an important analgesic and anti-inflammatory drug, widely used for the treatment of postoperative pain, rheumatoid arthritis, and chronic pain. Consequently, diclofenac is often used in combination regimens and undesirable drug-drug interactions may occur.
Voltaren®, 50 mg soluble tablets, was selected among other possible diclofenac products because with this formulation peak concentration of diclofenamic acid is achieved at approximately 1 h, i.e. in less than 2 h.
The present interaction study was designed in agreement with the FDA Guideline on Drug Interaction studies, taking also in consideration the EMA guideline on the Investigation of drug interactions.
- Conditions
- Healthy
- Being tested
- Diclofenac sodium, Diclofenac sodium and safinamide
- Keywords
- PK study
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Diclofenac sodiumDrug
Also called Voltaren
Diclofenac sodium 50 mg single dose
Diclofenac sodium and safinamideDrug
Also called Voltaren and Xadago
Diclofenac 50 mg single dose and safinamide 200 mg single dose
| Study group | Role | What they receive |
|---|---|---|
| Diclofenac sodium | Experimental | Diclofenac sodium 50 mg oral tablets, single dose Receives: Drug: Diclofenac sodium |
| Diclofenac sodium and safinamide | Active comparator | Diclofenac sodium 50 mg oral tablets, single dose, and safinamide 200 mg oral tablets, single dose Receives: Drug: Diclofenac sodium and safinamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
To Evaluate Plasma Diclofenamic Acid Extent of Exposure Reported as Plasma AUC After Single Administration of 50 mg Diclofenac Sodium, With and Without Co-administration of a Single 200 mg Dose of Safinamide.
Plasma diclofenamic acid AUC0-t after T2 single dose, with and without T1 co-administration. To measure AUC plasma samples were taken by the participants at different time points, and the concentrations of diclofenac and safinamide were measured. AUC0-t is the area under the concentration-time curve from administration to the last observed concentration time t; PK parameters AUC0-t were analysed using analysis of variance (ANOVA). Before analysis, the data were transformed using a neperian logarithmic transformation. ANOVA was performed taking into account treatment, period, sequence and subject (sequence) as fixed effects with a variance components structure of the covariance matrix.
Measured: 24 hours
Secondary outcomes (4)
Evaluate Diclofenac Rate of Absorption Reported as Plasma Cmax After Single Administration of 50 mg Diclofenac With and Without 200 mg of Safinamide.
Cmax, of plasma diclofenamic acid after T2 single dose, with and without T1 co-administration. The parametric point estimators (PE) for the ratios of T2 treatment with T1 co-administration / T2 treatment without T1 co-administration for the PK parameters under consideration, and the two-sided 90% confidence interval (CI), were calculated using the adjusted least squares means (LSMEANS) from the ANOVA. LSmeans differences obtained in the log scale for Cmax were back-transformed to obtain the PE (i.e. geometric mean ratio) and the two-sided 90% CI as percentages.
Measured: 24 hours
Tmax and T1/2
Measured: 24 hours
Lamda z
Measured: 24 hours
Relative Bioavailability (Frel)
calculated as ratio between AUC0-t (test) / AUC0-t (reference)
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2015 (estimated)
- Study startMay 2015
- Primary completionMay 2015
- Study completionMay 2015
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 HealthyStudies 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
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zambon SpA
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Cross Research S.A.
- Responsible party
- Sponsor
- Investigators
- Milko Radicioni, MD, Principal investigator, Cross Research SA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02495831
- Sponsor's protocol ID
- Z7219J01
- Status last verified
- Apr 2016
- First submitted
- 3 Jul 2015
- Last updated
- 15 Apr 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No: Bioequivalence data are to be considered as a whole in all subjects (90%CI).
Study at a glance
From the registry record, last updated by the sponsor on 15 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Drug Interaction Study of Safinamide and a BCRP Substrate, Diclofenac, Concomitantly Administered to Healthy Volunteers
- ClinicalTrials.gov ID
- NCT02495831
- Acronym / sponsor ID
- Z7219J01
- Conditions
- Healthy
- Keywords
- PK study
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Zambon SpAIndustry (pharma, biotech, devices)
- Collaborators
- Cross Research S.A.
- Study start
- May 2015
- Primary completion
- May 2015 (actual)
- Study completion
- May 2015 (actual)
- First posted
- 13 Jul 2015 (estimated)
- Results
- Posted 15 Apr 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To evaluate if a single dose of safinamide 200 mg has an effect on the pharmacokinetics of diclofenamic acid, concomitantly administered as a single 50 mg diclofenac sodium dose, with respect to 50 mg diclofenac sodium administered alone.
Detailed description
According to Xadago™ SmPC, safinamide may transiently inhibit BCRP, therefore a time interval of 5 h should be kept between dosing of safinamide and medicinal products that are BCRP substrates with a Tmax ≤2 h (e.g. diclofenac, pitavastatin, pravastatin, ciprofloxacin, methotrexate, topotecan or glyburide).
Following a specific request of EMA CHMP, the present interaction study in healthy male and female volunteers was conducted to determine if co-administration of safinamide with a BCRP substrate alters plasma exposure of the BCRP substrate in vivo.
Diclofenac was chosen among the other BCRP substrates considering its large use in the general population. Diclofenac in fact is an important analgesic and anti-inflammatory drug, widely used for the treatment of postoperative pain, rheumatoid arthritis, and chronic pain. Consequently, diclofenac is often used in combination regimens and undesirable drug-drug interactions may occur.
Voltaren®, 50 mg soluble tablets, was selected among other possible diclofenac products because with this formulation peak concentration of diclofenamic acid is achieved at approximately 1 h, i.e. in less than 2 h.
The present interaction study was designed in agreement with the FDA Guideline on Drug Interaction studies, taking also in consideration the EMA guideline on the Investigation of drug interactions.
Study design
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Diclofenac sodium | Experimental | Drug: Diclofenac sodiumDiclofenac sodium 50 mg oral tablets, single dose |
| Diclofenac sodium and safinamide | Active comparator | Drug: Diclofenac sodium and safinamideDiclofenac sodium 50 mg oral tablets, single dose, and safinamide 200 mg oral tablets, single dose |
Who may qualify
- Ages
- 22 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Signed written informed consent before inclusion in the study
- Males and females, 25-55 years old
- Body Mass Index (BMI): 18.5-30 kg/m2
- Systolic blood pressure 100-139 mmHg, diastolic blood pressure 50-89 mmHg, heart rate 50-90 bpm
- Ability to comprehend the full nature and purpose of the study
Key exclusion criteria (14 listed)
- Contraindications to MAO-B inhibitors, antiepileptic drugs, or to any NSAIDs
- Clinically significant abnormalities in ECG
- Clinically significant abnormal physical findings
- Clinically significant abnormal laboratory values
- Hypersensitivity or history of anaphylaxis to drugs or allergic reactions in general
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 |
|---|---|---|
| Diclofenac sodiumAlso: VoltarenDiclofenac sodium 50 mg single dose | Drug | Diclofenac sodium |
| Diclofenac sodium and safinamideAlso: Voltaren and XadagoDiclofenac 50 mg single dose and safinamide 200 mg single dose | Drug | Diclofenac sodium and safinamide |
Primary outcome
To Evaluate Plasma Diclofenamic Acid Extent of Exposure Reported as Plasma AUC After Single Administration of 50 mg Diclofenac Sodium, With and Without Co-administration of a Single 200 mg Dose of Safinamide.
Time frame: 24 hours
Plasma diclofenamic acid AUC0-t after T2 single dose, with and without T1 co-administration. To measure AUC plasma samples were taken by the participants at different time points, and the concentrations of diclofenac and safinamide were measured. AUC0-t is the area under the concentration-time curve from administration to the last observed concentration time t; PK parameters AUC0-t were analysed using analysis of variance (ANOVA). Before analysis, the data were transformed using a neperian logarithmic transformation. ANOVA was performed taking into account treatment, period, sequence and subject (sequence) as fixed effects with a variance components structure of the covariance matrix.
4 secondary outcomes
Evaluate Diclofenac Rate of Absorption Reported as Plasma Cmax After Single Administration of 50 mg Diclofenac With and Without 200 mg of Safinamide.
Time frame: 24 hours
Tmax and T1/2
Time frame: 24 hours
Lamda z
Time frame: 24 hours
Relative Bioavailability (Frel)
Time frame: 24 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Apr 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. Bioequivalence data are to be considered as a whole in all subjects (90%CI).
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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.
Milko Radicioni, MD principal investigator
Cross Research SA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Diclofenac sodium and Diclofenac sodium and safinamide in people with Healthy, run by Zambon SpA at 1 site in Switzerland.
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 14 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 15 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
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 15 Apr 2016). 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?
To Evaluate Plasma Diclofenamic Acid Extent of Exposure Reported as Plasma AUC After Single Administration of 50 mg Diclofenac Sodium, With and Without Co-administration of a Single 200 mg Dose of Safinamide. (time frame: 24 hours). 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 15 Apr 2016.