Effect of Repeated Dosing of Naproxcinod on Renal Hemodynamic and on Sodium Balance in Healthy Volunteers Before and After a Single Dose of Furosemide

NCT00909519 | Completed Phase 1

• 1 other identifier: HCT3012-X-113
• Study Type: interventional
• Target: 31
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase 1 study is an 8-day treatment period, randomized, controlled, double-blind, 3 parallel-groups, monocentric study. The primary objective is to evaluate the effect of naproxcinod on the renal function when co-administered with furosemide in comparison to naproxen and placebo.

Conditions

Renal Hemodynamics

Outcome Measures

Primary Outcomes (1)

• To evaluate the effect of naproxcinod on the renal function when co-administered with furosemide in comparison to naproxen and placebo

  Day 8, between H3 and H9

Secondary Outcomes (2)

• to assess the effect of naproxcinod on blood pressure (BP) in comparison with naproxen and placebo over 1 week and when co-administered with furosemide + to assess the general safety and tolerability

  for over 1 week

• To evaluate the effect of naproxcinod when administered alone on renal function, after a week of administration, in comparison with naproxen and placebo.

  Day 8 at H4

Study Arms (3)

naproxen

ACTIVE COMPARATOR

Drug: Naproxen

naproxcinod

EXPERIMENTAL

Drug: naproxcinod; Drug: furosemide

placebo

PLACEBO COMPARATOR

Drug: placebo

Interventions

naproxcinod DRUG

naproxcinod 750 mg bid

naproxcinod

Naproxen DRUG

Naproxen 500 mg bid

naproxen

placebo DRUG

placebo

placebo

furosemide DRUG

furosemide

naproxcinod

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy, non smoker male subjects aged 18 and 35 years (inclusive), at the Screening visit.
• Body Mass Index (BMI) strictly between 18 and 30 kg/m² (inclusive) with body weight≥ 50 kg at the Screening visit.
• Normal physical examination at the Screening visit.
• Normal ECG (12-lead) at the Screening visit, as judged by the Investigator.
• At Screening and run-in period visits , Systolic Blood Pressure (SBP) between 100 and 139 mmHg (inclusive) and Diastolic Blood Pressure (DBP) between 50 and 89 mmHg (inclusive).
• At Screening and run-in period visits, HR between 45 and 90 bpm (inclusive).
• Subjects must be able to understand the written information sheet and informed consent and comply with all study requirements.
• Subjects must provide a written, dated and signed informed consent prior to any study procedure.

You may not qualify if:

• A history of hypersensitivity reactions (such as asthma, rhinitis, or urticaria) to aspirin, naproxen or any other NSAIDs; or hypersensitivity or contraindications to organic nitrate drugs or hypersensitivity to furosemide or to sinistrine or PAH.
• Family history of hypertension which may disqualify the subject, as judged by the investigator..
• History of any clinically relevant gastrointestinal (such as gastritis or gastric ulcer), respiratory, psychiatric, neurologic, kidney, liver, cardiac disease, bleeding disorder, other disease/condition or abnormal physical finding which may interfere with the study objectives. The investigator may disqualify any subject for a sound medical or psychiatric reason.
• History or presence of ASAT \>40UI/L, ALAT \>40UI/L, serum bilirubin 3 times above the Upper Limit of Normal range at the Screening visit.
• Creatinine clearance inferior/equal to 80 ml/min as calculated with the Cockcroft-Gault formula (Appendix 5 of the protocol) at the Screening visit.
• Plasmatic potassium \<3.5 mmole/L at the Screening visit.
• Seropositivity for HBs, HBc, HIV 1 or HIV 2 at the Screening visit.
• Donations of blood, plasma or platelets within 3 months prior to the Screening visit or donation planned during the 3 months following Day 8.
• Any clinically significant abnormal laboratory values at the Screening visit.
• At the Screening visit, after 1 minute in a standing position, a drop of more than 20 mmHg in SBP or 10 mmHg in DBP or a clinical manifestation of postural hypotension.
• Chronic use of any drugs (prescription or OTC) within 4 weeks prior to Visit 2 (single use of medication such as paracetamol for headache will be tolerated at the lowest possible dose).
• Intake of any Nitric Oxide Synthase Inhibitor within 1 month before Screening visit.
• History of drug addiction or alcohol abuse as defined by DSM IVR, diagnostic criteria for drug and alcohol abuse or drug addiction.
• Positive drug screening (opiates, cannabinoids, cocaine, benzodiazepines, amphetamines, barbiturates) at the Screening visit.
• Current participation or participation within 60 days prior to the Screening visit, in another investigational study, including the present study or any previous enrolment in a naproxcinod study.

Sponsors & Collaborators

• NicOx: lead

MeSH Terms

Interventions

naproxen-n-butyl nitrate; Naproxen; Furosemide

Intervention Hierarchy (Ancestors)

Naphthaleneacetic Acids; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Sulfanilamides; Sulfonamides; Amides; Aniline Compounds; Amines; Sulfones; Sulfur Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: May 27, 2009
• First Posted: May 28, 2009
• Study Start: January 1, 2009
• Primary Completion: April 1, 2009
• Study Completion: April 1, 2009
• Last Updated: June 17, 2011

Record last verified: 2011-06