Drug Interaction Study of Safinamide and a BCRP Substrate, Diclofenac, Concomitantly Administered to Healthy Volunteers
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|ClinicalTrials.gov Identifier: NCT02495831|
Recruitment Status : Completed
First Posted : July 13, 2015
Results First Posted : April 15, 2016
Last Update Posted : April 15, 2016
|Condition or disease||Intervention/treatment||Phase|
|Healthy||Drug: Diclofenac sodium Drug: Diclofenac sodium and safinamide||Phase 1|
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||24 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||None (Open Label)|
|Official Title:||Drug Interaction Study of Safinamide and a BCRP Substrate, Diclofenac, Concomitantly Administered to Healthy Volunteers|
|Study Start Date :||May 2015|
|Actual Primary Completion Date :||May 2015|
|Actual Study Completion Date :||May 2015|
Experimental: Diclofenac sodium
Diclofenac sodium 50 mg oral tablets, single dose
Drug: Diclofenac sodium
Diclofenac sodium 50 mg single dose
Other Name: Voltaren
Active Comparator: Diclofenac sodium and safinamide
Diclofenac sodium 50 mg oral tablets, single dose, and safinamide 200 mg oral tablets, single dose
Drug: Diclofenac sodium and safinamide
Diclofenac 50 mg single dose and safinamide 200 mg single dose
Other Name: Voltaren and Xadago
- 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.
- 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 ]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.
- Tmax and T1/2 [ Time Frame: 24 hours ]
- Lamda z [ Time Frame: 24 hours ]
- Relative Bioavailability (Frel) [ Time Frame: 24 hours ]calculated as ratio between AUC0-t (test) / AUC0-t (reference)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02495831
|Cross Research SA, Phase I Unit|
|Arzo, Ticino, Switzerland, 6864|
|Principal Investigator:||Milko Radicioni, MD||Cross Research SA|