HealthyPhase 1NCT03216304
Safinamide Steady State Interaction With Rosuvastatin
A Phase 1 study testing 100 mg safinamide, 20 mg rosuvastatin calcium period 1 and 20 mg rosuvastatin calcium period 2 in people with Healthy, run by Cross Research S.A. at 1 site in Switzerland.
Trial summary
To evaluate if safinamide at the steady state, obtained after multiple 100 mg once a day administrations, has an effect on the pharmacokinetics of rosuvastatin, concomitantly administered as a single 20 mg dose, with respect to the pharmacokinetics of 20 mg rosuvastatin administered alone. Read more about this study
- Who is it for?
- Ages 25 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- 100 mg safinamide, 20 mg rosuvastatin calcium period 1 and 20 mg rosuvastatin calcium period 2
- 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
- 22 May 2017to 6 Jul 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 25 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Informed consent: signed written informed consent before inclusion in the study
- Sex and age: males and females, 25-55 years old, inclusive
- Body Mass Index (BMI): 18.5-30 kg/m2, inclusive
- Vital signs: systolic blood pressure (SBP) 100-139 mmHg, diastolic blood pressure (DBP) 50-89 mmHg, heart rate (HR) 50-90 bpm, measured after 5 min of rest in the sitting position
- Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the investigator and to comply with the requirements of the entire study
- Contraception and fertility (females only): females of child-bearing potential and with an active sexual life must be using at least one of the following reliable methods of contraception:
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- 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 agrees 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 will be admitted.
- For all female subjects, pregnancy test result must be negative at screening (serum β-HCG test) and day -3 (urine test).
Who cannot join
- Contraindications: contraindications to monoamine oxidase-B (MAO-B) inhibitors, antiepileptic drugs, statins and HMG-CoA reductase inhibitors
- Origin: Asian subjects
- Electrocardiogram (ECG 12-leads, supine position): clinically significant abnormalities
- Physical findings: clinically significant abnormal physical findings which could interfere with the objectives of the study; albinism
- Laboratory analyses: clinically significant abnormal laboratory values indicative of physical illness
- Allergy: ascertained or presumptive hypersensitivity to the active principles and/or formulations' ingredients; hypersensitivity or history of anaphylaxis to drugs or allergic reactions in general, which the investigator considers may affect the outcome of the study. Subjects with rare hereditary problems of galactose intolerance, the Lapp lactose deficiency or glucose-galactose malabsorption
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- Diseases: significant history of renal, hepatic, gastrointestinal, cardiovascular, respiratory, skin, haematological, endocrine, neurological or musculoskeletal diseases that may interfere with the aim of the study
- Medications: medications, including over the counter medications and herbal remedies, for 2 weeks before the start of the study. In particular statins and HMG-CoA reductase inhibitors in the 4 weeks before the screening visit; medicinal products that are BCRP substrates; ciclosporin, protease inhibitors, gemfibrozil and other lipid-lowering products, ezetimibe, antacid containing aluminium and magnesium hydroxide, erythromycin and other medicinal products according to the information reported in rosuvastatin SmPC, in the 4 weeks before the screening visit; treatment with morphine or other similar opioids, whose concomitant use with MAO-B inhibitors is contraindicated, SSRIs, SNRIs, tri- or tetracyclic antidepressant, tramadol, pethidine, dextromethorphan, MAO inhibitors (e.g. selegiline), meperidine derivatives and antiepileptic drugs in the 4 weeks before the screening visit; treatment with any known enzyme inhibiting or inducing agent within 4 weeks preceding the screening visit. Hormonal contraceptives
- Investigative drug studies: participation in the evaluation of any investigational product for 3 months before this study. The 3-month interval is calculated as the time between the first calendar day of the month that follows the last visit of the previous study and the first day of the present study
- Blood donation: blood donations for 3 months before this study
- Drug, alcohol, caffeine, tobacco: history of drug, alcohol [>1 drink/day for females and >2 drinks/day for males, defined according to the USDA Dietary Guidelines 2015-2020], caffeine (>5 cups coffee/tea/day) or tobacco abuse (≥10 cigarettes/day)
- Drug test: positive drug test at screening or day -3
- Alcohol breath test: positive alcohol breath test at day -3
- Diet: abnormal diets (<1600 or >3500 kcal/day) or substantial changes in eating habits in the 4 weeks before this study; vegetarians; intake of alcohol, grapefruit or grapefruit juice, apple or orange juice, vegetables from the mustard green family (e.g., kale, broccoli, watercress, collard greens, kohlrabi, brussels sprouts, mustard), and charbroiled meats for 1 week before the start of the study
- Pregnancy (females only): positive or missing pregnancy test at screening or day -3, 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
Official title: Drug Interaction Study of Safinamide and a BCRP Substrate, Rosuvastatin, Concomitantly Administered to Healthy Volunteers
To evaluate if safinamide at the steady state, obtained after multiple 100 mg once a day administrations, has an effect on the pharmacokinetics of rosuvastatin, concomitantly administered as a single 20 mg dose, with respect to the pharmacokinetics of 20 mg rosuvastatin administered alone.
Read the detailed description
Xadago® SmPC reports that 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. pitavastatin, pravastatin, ciprofloxacin, methotrexate, topotecan, diclofenac or glyburide).
Following a specific request of FDA, the present interaction study in healthy male and female volunteers will be conducted in order to determine if multiple dose administration of safinamide with the BCRP substrate rosuvastatin alters the plasma exposure of rosuvastatin in vivo. Orally administered rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, developed for the treatment of dyslipidaemia, represents a sensitive probe to assess the magnitude of BCRP inhibition. In PK trials in healthy volunteers, rosuvastatin Tmax ranged from 1.7 to 5 h after administration of 10-80 mg doses.
- Conditions
- Healthy
- Being tested
- 100 mg safinamide, 20 mg rosuvastatin calcium period 1, 20 mg rosuvastatin calcium period 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
100 mg safinamideDrug
Also called Xadago®
Safinamide will be administered as follows:
- Days 5-11: 100 mg safinamide (one Xadago® tablet), once a day
- Day 12: a single dose of 100 mg safinamide (one Xadago® tablet), immediately followed by a single dose of 20 mg rosuvastatin calcium (one Crestor® tablet)
- Days 13-15: 100 mg safinamide (one Xadago® tablet) once a day The medication will be orally administered in the morning, at 8:00±1h, under fasting conditions, with 240 mL (total volume) of still mineral water.
20 mg rosuvastatin calcium period 1Drug
Also called Crestor®
Rosuvastatin will be administered as follows:
- Day 1: a single dose of 20 mg rosuvastatin calcium (one Crestor® tablet)
20 mg rosuvastatin calcium period 2Drug
Also called Crestor®
- Day 12: a single dose of 20 mg rosuvastatin calcium (one Crestor® tablet) immediately after the safinamide administration
| Study group | Role | What they receive |
|---|---|---|
| rosuvastatin | Experimental | Film-coated tablets Rosuvastatin will be administered at the dose of 20 mg (single dose at day 1) Receives: Drug: 20 mg rosuvastatin calcium period 1 |
| safinamide + rosuvastatin | Experimental | Film-coated tablets Safinamide will be administered at the dose 100 mg (once a day for 11 days) Film-coated tablets Rosuvastatin will be administered at the dose of 20 mg (single dose at 12) Receives: Drug: 100 mg safinamide; Drug: 20 mg rosuvastatin calcium period 2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Transporter-Mediated Interaction (TMI) between safinamide (investigational drug) and rosuvastatin (selected BCRP substrate) defined as ANOVA comparison between AUC of treatments (co-administration / rosuvastatin alone)
Transporter-Mediated Interaction (TMI) between safinamide (investigational drug) and rosuvastatin (selected BCRP substrate) evaluated after the FDA - CDER Draft Guidance on Drug Interaction Studies of February 2012. Blood samples will be collected at different time points up to 96 h and the concentrations of rosuvastatin will be measured after single administration of a 20 mg dose with and without co-administration of multiple 100 mg doses of safinamide in a cross-over design. The Area Under the Curve (AUC), calculated with a non-compartmental method will be used as metrics for the plasma rosuvastatin extent of exposure. The parametric point estimators (PEs) for the ratios of treatments (co-administration / rosuvastatin alone) and the 90% confidence intervals will be calculated using the adjusted least squares means (LSMEANS) from an Analysis of variance (ANOVA) on rosuvastatin AUC. Presence of a TMI will be defined as an upper limit of the 90% confidence interval above 125.00.
Measured: 96 hours
Secondary outcomes (3)
Transporter-Mediated Interaction (TMI) between safinamide (investigational drug) and rosuvastatin (selected BCRP substrate) defined as ANOVA comparison between Cmax of treatments (co-administration / rosuvastatin alone)
Transporter-Mediated Interaction (TMI) between safinamide (investigational drug) and rosuvastatin (selected BCRP substrate). Blood samples will be collected at different time points up to 96 h and the concentrations of rosuvastatin will be measured after single administration of a 20 mg dose with and without co-administration of multiple 100 mg doses of safinamide in a cross-over design. The Peak Concentration (Cmax), calculated with a non-compartmental method will be used as one of the metrics for the plasma rosuvastatin rate of exposure. Secondary criteria for TMI presence will be the same as for the AUC.
Measured: 96 hours
Transporter-Mediated Interaction (TMI) between safinamide (investigational drug) and rosuvastatin (selected BCRP substrate) defined as as non-parametric comparison between Tmax of treatments (co-administration / rosuvastatin alone)
Transporter-Mediated Interaction (TMI) between safinamide (investigational drug) and rosuvastatin (selected BCRP substrate). Blood samples will be collected at different time points up to 96 h and the concentrations of rosuvastatin will be measured after single administration of a 20 mg dose with and without co-administration of multiple 100 mg doses of safinamide in a cross-over design. The Time to the Peak Concentration (Tmax), calculated with a non-compartmental method will be used as one of the metrics for the plasma rosuvastatin rate of exposure. Secondary criteria for TMI presence interaction will be a significant p-value (i.e. >0.05) obtained from a non-parametric Wilcoxon signed-rank test on the Tmax parameter.
Measured: 96 hours
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Treatment emergent adverse events (TEAEs), vital signs (blood pressure and heart rate), body weight, electrocardiogram and laboratory parameters will be considered for safety and tolerability assessments.
Measured: 96 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 2017
- Study start22 May 2017
- Primary completion6 Jul 2017
- Study completion6 Jul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cross Research S.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Zambon SpA
- Responsible party
- Principal investigator, Milko Radicioni, Cross Research S.A.
- Investigators
- Milko Radicioni, MD, Principal investigator, CROSS Research SA, Phase I Unit, Via FA Giorgioli 12, 6864 Arzo Switzerland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03216304
- Sponsor's protocol ID
- Z7219J02
- Status last verified
- Jun 2017
- First submitted
- 1 Jun 2017
- Last updated
- 1 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Drug Interaction Study of Safinamide and a BCRP Substrate, Rosuvastatin, Concomitantly Administered to Healthy Volunteers
- ClinicalTrials.gov ID
- NCT03216304
- Acronym / sponsor ID
- Z7219J02
- Conditions
- Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Cross Research S.A.Industry (pharma, biotech, devices)
- Collaborators
- Zambon SpA
- Study start
- 22 May 2017 (actual)
- Primary completion
- 6 Jul 2017 (actual)
- Study completion
- 6 Jul 2017 (actual)
- First posted
- 13 Jul 2017 (actual)
- Results
- Not posted in the source record
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 safinamide at the steady state, obtained after multiple 100 mg once a day administrations, has an effect on the pharmacokinetics of rosuvastatin, concomitantly administered as a single 20 mg dose, with respect to the pharmacokinetics of 20 mg rosuvastatin administered alone.
Detailed description
Xadago® SmPC reports that 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. pitavastatin, pravastatin, ciprofloxacin, methotrexate, topotecan, diclofenac or glyburide).
Following a specific request of FDA, the present interaction study in healthy male and female volunteers will be conducted in order to determine if multiple dose administration of safinamide with the BCRP substrate rosuvastatin alters the plasma exposure of rosuvastatin in vivo. Orally administered rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, developed for the treatment of dyslipidaemia, represents a sensitive probe to assess the magnitude of BCRP inhibition. In PK trials in healthy volunteers, rosuvastatin Tmax ranged from 1.7 to 5 h after administration of 10-80 mg doses.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| rosuvastatin | Experimental | Drug: 20 mg rosuvastatin calcium period 1Film-coated tablets Rosuvastatin will be administered at the dose of 20 mg (single dose at day 1) |
| safinamide + rosuvastatin | Experimental | Drug: 100 mg safinamide, Drug: 20 mg rosuvastatin calcium period 2Film-coated tablets Safinamide will be administered at the dose 100 mg (once a day for 11 days) Film-coated tablets Rosuvastatin will be administered at the dose of 20 mg (single dose at 12) |
Who may qualify
- Ages
- 25 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Informed consent: signed written informed consent before inclusion in the study
- Sex and age: males and females, 25-55 years old, inclusive
- Body Mass Index (BMI): 18.5-30 kg/m2, inclusive
- Vital signs: systolic blood pressure (SBP) 100-139 mmHg, diastolic blood pressure (DBP) 50-89 mmHg, heart rate (HR) 50-90 bpm, measured after 5 min of rest in the sitting position
- Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the investigator and to comply with the requirements of the entire study
Key exclusion criteria (15 listed)
- Contraindications: contraindications to monoamine oxidase-B (MAO-B) inhibitors, antiepileptic drugs, statins and HMG-CoA reductase inhibitors
- Origin: Asian subjects
- Electrocardiogram (ECG 12-leads, supine position): clinically significant abnormalities
- Physical findings: clinically significant abnormal physical findings which could interfere with the objectives of the study; albinism
- Laboratory analyses: clinically significant abnormal laboratory values indicative of physical illness
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 |
|---|---|---|
| 100 mg safinamideAlso: Xadago®Safinamide will be administered as follows: * Days 5-11: 100 mg safinamide (one Xadago® tablet), once a day * Day 12: a single dose of 100 mg safinamide (one Xadago® tablet), immediately followed by a single dose of 20 mg rosuvastatin calcium (one Crestor® tablet) * Days 13-15: 100 mg safinamide (one Xadago® tablet) once a day The medication will be orally administered in the morning, at 8:00±1h, under fasting conditions, with 240 mL (total volume) of still mineral water. | Drug | safinamide + rosuvastatin |
| 20 mg rosuvastatin calcium period 1Also: Crestor®Rosuvastatin will be administered as follows: - Day 1: a single dose of 20 mg rosuvastatin calcium (one Crestor® tablet) | Drug | rosuvastatin |
| 20 mg rosuvastatin calcium period 2Also: Crestor®- Day 12: a single dose of 20 mg rosuvastatin calcium (one Crestor® tablet) immediately after the safinamide administration | Drug | safinamide + rosuvastatin |
Primary outcome
Transporter-Mediated Interaction (TMI) between safinamide (investigational drug) and rosuvastatin (selected BCRP substrate) defined as ANOVA comparison between AUC of treatments (co-administration / rosuvastatin alone)
Time frame: 96 hours
Transporter-Mediated Interaction (TMI) between safinamide (investigational drug) and rosuvastatin (selected BCRP substrate) evaluated after the FDA - CDER Draft Guidance on Drug Interaction Studies of February 2012. Blood samples will be collected at different time points up to 96 h and the concentrations of rosuvastatin will be measured after single administration of a 20 mg dose with and without co-administration of multiple 100 mg doses of safinamide in a cross-over design. The Area Under the Curve (AUC), calculated with a non-compartmental method will be used as metrics for the plasma rosuvastatin extent of exposure. The parametric point estimators (PEs) for the ratios of treatments (co-administration / rosuvastatin alone) and the 90% confidence intervals will be calculated using the adjusted least squares means (LSMEANS) from an Analysis of variance (ANOVA) on rosuvastatin AUC. Presence of a TMI will be defined as an upper limit of the 90% confidence interval above 125.00.
3 secondary outcomes
Transporter-Mediated Interaction (TMI) between safinamide (investigational drug) and rosuvastatin (selected BCRP substrate) defined as ANOVA comparison between Cmax of treatments (co-administration / rosuvastatin alone)
Time frame: 96 hours
Transporter-Mediated Interaction (TMI) between safinamide (investigational drug) and rosuvastatin (selected BCRP substrate) defined as as non-parametric comparison between Tmax of treatments (co-administration / rosuvastatin alone)
Time frame: 96 hours
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time frame: 96 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2017.
- CROSS ResearchLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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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, Phase I Unit, Via FA Giorgioli 12, 6864 Arzo Switzerland
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 100 mg safinamide, 20 mg rosuvastatin calcium period 1 and 20 mg rosuvastatin calcium period 2 in people with Healthy, run by Cross Research S.A. 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 10 inclusion and 15 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 1 Aug 2017. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Transporter-Mediated Interaction (TMI) between safinamide (investigational drug) and rosuvastatin (selected BCRP substrate) defined as ANOVA comparison between AUC of treatments (co-administration / rosuvastatin alone) (time frame: 96 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 1 Aug 2017.