Trial Outcomes & Findings for Drug Interaction Study of Safinamide and a BCRP Substrate, Diclofenac, Concomitantly Administered to Healthy Volunteers (NCT NCT02495831)

Last Updated: 2016-04-15

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

24 participants

Primary outcome timeframe

24 hours

Results posted on

2016-04-15

Participant Flow

The recruitment started and finished on May 2015 and the study was performed in Switzerland at CROSS Research S.A., Phase I Unit, Via F.A. Giorgioli 14 CH-6864 Arzo, Switzerland

Twenty-four (24) subjects were randomised in the study. One of the 24 subjects discontinued the study before study treatment. Twenty-two (22) subjects completed the study per protocol.

Participant milestones

Participant milestones
Measure	Diclofenac Sodium First, Safinamide + Diclofenac Sodium Second Diclofenac sodium 50 mg oral tablets, single dose, and safinamide 200 mg oral tablets, single dose	Safinamide + Diclofenac Sodium First, Diclofenac Sodium Second Diclofenac sodium 50 mg oral tablets, single dose Safinamide 200 mg oral tablets, single dose
First Intervention STARTED	13	10
First Intervention COMPLETED	13	10
First Intervention NOT COMPLETED	0	0
Second Intervention STARTED	12	10
Second Intervention COMPLETED	12	10
Second Intervention NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Drug Interaction Study of Safinamide and a BCRP Substrate, Diclofenac, Concomitantly Administered to Healthy Volunteers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Intervention n=23 Participants Diclofenac sodium 50 mg oral tablets, single dose Diclofenac sodium 50 mg oral tablets, single dose and safinamide 200 mg oral tablets, single dose
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	23 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	41.6 years STANDARD_DEVIATION 9.1 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	23 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment Switzerland	23 participants n=5 Participants

PRIMARY outcome

Timeframe: 24 hours

Population: healthy volunteers

Outcome measures

Outcome measures
Measure	Diclofenac Sodium n=22 Participants Diclofenac sodium 50 mg oral tablets, single dose Diclofenac sodium: Diclofenac sodium 50 mg single dose	Diclofenac Sodium and Safinamide n=22 Participants Diclofenac sodium 50 mg oral tablets, single dose, and safinamide 200 mg oral tablets, single dose Diclofenac sodium and safinamide: Diclofenac 50 mg single dose and safinamide 200 mg single dose
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.	1323.28 h X ng per mL Standard Deviation 390.53	1381.32 h X ng per mL Standard Deviation 393.77

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Diclofenac Sodium n=22 Participants Diclofenac sodium 50 mg oral tablets, single dose Diclofenac sodium: Diclofenac sodium 50 mg single dose	Diclofenac Sodium and Safinamide n=22 Participants Diclofenac sodium 50 mg oral tablets, single dose, and safinamide 200 mg oral tablets, single dose Diclofenac sodium and safinamide: Diclofenac 50 mg single dose and safinamide 200 mg single dose
Evaluate Diclofenac Rate of Absorption Reported as Plasma Cmax After Single Administration of 50 mg Diclofenac With and Without 200 mg of Safinamide.	766.59 ng/mL Standard Deviation 390.01	833.50 ng/mL Standard Deviation 443.34

SECONDARY outcome

Timeframe: 24 hours

Outcome measures

Outcome measures
Measure	Diclofenac Sodium n=22 Participants Diclofenac sodium 50 mg oral tablets, single dose Diclofenac sodium: Diclofenac sodium 50 mg single dose	Diclofenac Sodium and Safinamide n=22 Participants Diclofenac sodium 50 mg oral tablets, single dose, and safinamide 200 mg oral tablets, single dose Diclofenac sodium and safinamide: Diclofenac 50 mg single dose and safinamide 200 mg single dose
Tmax and T1/2 Tmax	0.88 hours Standard Deviation 0.41	1.0 hours Standard Deviation 0.43
Tmax and T1/2 T1/2	1.24 hours Standard Deviation 0.43	1.19 hours Standard Deviation 0.40

SECONDARY outcome

Timeframe: 24 hours

Outcome measures

Outcome measures
Measure	Diclofenac Sodium n=22 Participants Diclofenac sodium 50 mg oral tablets, single dose Diclofenac sodium: Diclofenac sodium 50 mg single dose	Diclofenac Sodium and Safinamide n=22 Participants Diclofenac sodium 50 mg oral tablets, single dose, and safinamide 200 mg oral tablets, single dose Diclofenac sodium and safinamide: Diclofenac 50 mg single dose and safinamide 200 mg single dose
Lamda z	0.63 1/hours Standard Deviation 0.22	0.63 1/hours Standard Deviation 0.16

SECONDARY outcome

Timeframe: 24 hours

calculated as ratio between AUC0-t (test) / AUC0-t (reference)

Outcome measures

Outcome measures
Measure	Diclofenac Sodium n=22 Participants Diclofenac sodium 50 mg oral tablets, single dose Diclofenac sodium: Diclofenac sodium 50 mg single dose	Diclofenac Sodium and Safinamide n=22 Participants Diclofenac sodium 50 mg oral tablets, single dose, and safinamide 200 mg oral tablets, single dose Diclofenac sodium and safinamide: Diclofenac 50 mg single dose and safinamide 200 mg single dose
Relative Bioavailability (Frel)	107.67 ratio Standard Deviation 28.84	109.61 ratio Standard Deviation 32.14

Adverse Events

Diclofenac Sodium

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Diclofenac Sodium and Safinamide

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Milko Radicioni

CROSS REsearch SA

Phone: +41.91.63.00

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60