Pharmacokinetics Study: Determination of Naproxcinod and Its Metabolites After Oral Administration in Male

NCT01404598 | Completed Phase 1

• 1 other identifier: HCT 3012-X-114
• Study Type: interventional
• Target: 24
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study will be performed in 2 parts conducted in parallel: Part 1 (conducted on 16 healthy subjects): Administration of naproxcinod 750 mg or naproxen 500 mg twice a day (bid) during 7 days The main aim of this study part will be to assess the pharmacokinetic profile (i.e. the absorption, the distribution, the metabolism and the elimination of the drug after its administration) of nitrates (metabolite of naproxcinod) present in plasma, saliva and urine after oral administration of naproxcinod 750 mg bid for 7 days or naproxen 500 mg bid for 7 days as a reference. Part 2 (conducted on 8 healthy subjects): Administration of a single dose of naproxcinod 3000 mg. The main aim of this study part will be to assess the pharmacokinetic profile (i.e. the absorption, the distribution, the metabolism and the elimination of the drug after its administration) of Gamma-Hydroxybutyric Acid (GHB), a compound resulting from the transformation of the naproxcinod, after oral administration of a single supratherapeutic dose of 3000 mg.

Conditions

Pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• Part 1 : PK profile in plasma, saliva and urine : determination of nitrate levels.

  from Day 1 morning to Day 7 morning .

• Part 2 : PK profile in plasma : assess the Gamma-Hydroxybutyric acid (GHB) levels

  Day 1 to Day 4

Secondary Outcomes (12)

• Part 1: PK profile in saliva : determination of nitrite levels

  from Day 1 morning to Day 7 morning .

• Part 2 : PK profile in plasma : determination of nitrate levels

  Day 1 to Day 4

• Part 1 : PK profile in plasma : determination of Gamma-Hydroxybutyric acid (GHB) levels

  from Day 1 morning to Day 7 morning

• Part 1 : PK profile in plasma : determination of 1,4-butanediol mononitrate (BDMN) levels

  from Day 1 morning to Day 7 morning

• Part 1 : PK profile in plasma : determination of naproxcinod levels

  from Day 1 morning to Day 7 morning

Study Arms (3)

naproxcinod 750 mg bid

EXPERIMENTAL

Drug: naproxcinod 750 bid

naproxcinod 3000 mg od

EXPERIMENTAL

Drug: naproxcinod 3000 mg od

naproxen 500 mg bid

ACTIVE COMPARATOR

Drug: naproxen 500 mg bid

Interventions

naproxcinod 750 bid DRUG

naproxcinod 750 bid

naproxcinod 750 mg bid

naproxcinod 3000 mg od DRUG

naproxcinod 3000 mg od

naproxcinod 3000 mg od

naproxen 500 mg bid DRUG

naproxen 500 mg bid

naproxen 500 mg bid

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy, non smoker male subjects aged 18 to 45 years (inclusive).
• Body Mass Index (BMI) between 18 and 30 kg/m² (inclusive) with body weight (BW) ≥ 50 kg.
• Normal physical examination (non clinically significant abnormalities), as judged by the investigator.
• Normal electrocardiogram (ECG) (12-lead), (non clinically significant abnormalities), as judged by the Investigator.
• Supine Systolic Blood Pressure (SBP) between 100 and 139 mmHg (inclusive) and Diastolic Blood Pressure (DBP) between 50 and 89 mmHg (inclusive) (mean of 3 measurements).
• Supine Heart Rate (HR) between 45 and 90 bpm (inclusive).
• Oral body temperature (BT) between 36 and 37.5°C (inclusive).
• Subject must be able to understand the written information sheet and informed consent and comply with all study requirements.
• Subject must provide a written, dated and signed informed consent prior to any study procedure.

You may not qualify if:

• History of hypersensitivity reactions (such as asthma, rhinitis, or urticaria) to aspirin, naproxen or any other non steroidal anti-inflammatory drugs (NSAIDs); or hypersensitivity or contraindications to organic nitrate drugs; or to L-proline.
• 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, as judged by the Investigator.
• After 1 minute in a standing position, a drop of more than 20 mmHg in SBP or 10 mmHg in DBP compared to supine position (mean of 3 measurements) and a clinical manifestation of postural hypotension.
• Any clinically significant abnormal laboratory values, including creatinine clearance ≤ 80 mL/min as calculated with the Cockcroft-Gault formula.
• Seropositivity for HBs Ag, HCV Ab, HIV 1 or HIV 2 Ab.
• Any history of alcohol or drug abuse, or addiction within the last 2 years prior to enrollment.
• Positive drug screening (opiates, cannabinoids, cocaine, methadone, amphetamines, barbiturates, ecstasy).
• Positive alcohol or cotinine test.
• Donation of blood, plasma or platelets within 3 months prior to the Screening visit or donation planned during the 3 months following the study.
• Regular consumption of grapefruit juice or beverages containing xanthine bases (coffee, tea, cola: more than 5 cups or glasses a day).
• Current smokers or smoking history \< 6 months.
• Current participation or participation within 3 months prior to the Screening visit, in another investigational drug or device study, or previous enrolment in the present study.
• Chronic use of any drugs (prescription or over the counter \[OTC\]) within 4 weeks prior to enrollment (single use of medication such as paracetamol for headache is allowed, except during the week before enrollment).
• Use of antioxidant vitamin supplements within 1 week prior to enrollment.
• Use of mouthwash or toothpaste containing chlorhexidine within 1 week prior to randomization (applicable only for study Part 1).

Sponsors & Collaborators

• NicOx: lead

Related Links

• Nicox web-site

MeSH Terms

Interventions

naproxen-n-butyl nitrate; Naproxen; BID protein, human

Intervention Hierarchy (Ancestors)

Naphthaleneacetic Acids; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Antonio Rusca, MD FMH

  Cross Research S.A. Phase I Unit

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: June 16, 2011
• First Posted: July 28, 2011
• Study Start: January 1, 2010
• Primary Completion: February 1, 2010
• Study Completion: February 1, 2010
• Last Updated: August 11, 2011

Record last verified: 2011-08