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

NCT ID: NCT02495831

Last Updated: 2016-04-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-05-31
• Study Completion Date: 2015-05-31

Brief 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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Blinding Strategy: NONE

Study Groups

Diclofenac sodium

Diclofenac sodium 50 mg oral tablets, single dose

Group Type: EXPERIMENTAL

Diclofenac sodium

Intervention Type: DRUG

Diclofenac sodium 50 mg single dose

Diclofenac sodium and safinamide

Diclofenac sodium 50 mg oral tablets, single dose, and safinamide 200 mg oral tablets, single dose

Group Type: ACTIVE_COMPARATOR

Diclofenac sodium and safinamide

Intervention Type: DRUG

Diclofenac 50 mg single dose and safinamide 200 mg single dose

Interventions

Diclofenac sodium

Diclofenac sodium 50 mg single dose

Intervention Type: DRUG

Diclofenac sodium and safinamide

Diclofenac 50 mg single dose and safinamide 200 mg single dose

Intervention Type: DRUG

Other Intervention Names

Voltaren; Voltaren and Xadago

Eligibility Criteria

Inclusion Criteria

1. Signed written informed consent before inclusion in the study

2. Males and females, 25-55 years old

3. Body Mass Index (BMI): 18.5-30 kg/m2

4. Systolic blood pressure 100-139 mmHg, diastolic blood pressure 50-89 mmHg, heart rate 50-90 bpm

5. Ability to comprehend the full nature and purpose of the study

6. 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.

Exclusion Criteria

1. Contraindications to MAO-B inhibitors, antiepileptic drugs, or to any NSAIDs

2. Clinically significant abnormalities in ECG

3. Clinically significant abnormal physical findings

4. Clinically significant abnormal laboratory values

5. Hypersensitivity or history of anaphylaxis to drugs or allergic reactions in general

6. Significant history of renal, hepatic, gastrointestinal, cardiovascular, respiratory, skin, haematological, endocrine or neurological diseases

7. 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.

8. Participation in the evaluation of any investigational product for 3 months before the study.

9. Blood donations for 3 months before the study

10. History of drug, alcohol, caffeine or tobacco abuse

11. Positive drug test at screening or day -1

12. Positive alcohol breath test at day -1

13. Abnormal diets or substantial changes in eating habits in the 4 weeks before the study; vegetarians

14. Positive or missing pregnancy test at screening or day -1, pregnant or lactating women

• Minimum Eligible Age: 22 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Cross Research S.A.

INDUSTRY

Sponsor Role: collaborator

Zambon SpA

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Milko Radicioni, MD

Role: PRINCIPAL_INVESTIGATOR

Cross Research SA

Locations

Cross Research SA, Phase I Unit

Arzo, Canton Ticino, Switzerland

Countries

Switzerland

Other Identifiers

Z7219J01

Identifier Type: -

Identifier Source: org_study_id