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

This study has been completed.
Sponsor:
Information provided by:
NicOx
ClinicalTrials.gov Identifier:
NCT01404598
First received: June 16, 2011
Last updated: August 10, 2011
Last verified: August 2011
  Purpose

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.


Condition Intervention Phase
Pharmacokinetics
Drug: naproxcinod 750 bid
Drug: naproxcinod 3000 mg od
Drug: naproxen 500 mg bid
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: A Phase 1 Study to Assess the Pharmacokinetics of Nitrates and Gamma-Hydroxybutyric Acid (GHB) After Oral Administration of Therapeutic and Supratherapeutic Doses of Naproxcinod in Healthy Male Subjects

Resource links provided by NLM:


Further study details as provided by NicOx:

Primary Outcome Measures:
  • Part 1 : PK profile in plasma, saliva and urine : determination of nitrate levels. [ Time Frame: from Day 1 morning to Day 7 morning . ] [ Designated as safety issue: No ]
  • Part 2 : PK profile in plasma : assess the Gamma-Hydroxybutyric acid (GHB) levels [ Time Frame: Day 1 to Day 4 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Part 1: PK profile in saliva : determination of nitrite levels [ Time Frame: from Day 1 morning to Day 7 morning . ] [ Designated as safety issue: No ]
  • Part 2 : PK profile in plasma : determination of nitrate levels [ Time Frame: Day 1 to Day 4 ] [ Designated as safety issue: No ]
  • Part 1 : PK profile in plasma : determination of Gamma-Hydroxybutyric acid (GHB) levels [ Time Frame: from Day 1 morning to Day 7 morning ] [ Designated as safety issue: No ]
  • Part 1 : PK profile in plasma : determination of 1,4-butanediol mononitrate (BDMN) levels [ Time Frame: from Day 1 morning to Day 7 morning ] [ Designated as safety issue: No ]
  • Part 1 : PK profile in plasma : determination of naproxcinod levels [ Time Frame: from Day 1 morning to Day 7 morning ] [ Designated as safety issue: No ]
  • Part 1 : PK profile in plasma : determination of naproxen levels [ Time Frame: from Day 1 morning to Day 7 morning ] [ Designated as safety issue: No ]
  • Part 1 : PK profile in urine : determination of nitrosoproline levels [ Time Frame: from Day 1 morning to Day 7 morning ] [ Designated as safety issue: No ]
  • Part 1 : assess the general safety and tolerability [ Time Frame: from Day 1 morning to Day 7 morning ] [ Designated as safety issue: No ]
  • Part 2 : PK profile in plasma: determination of BDMN levels [ Time Frame: Day 1 to Day 4 ] [ Designated as safety issue: No ]
  • Part 2 : PK profile in plasma : determination of naproxcinod levels [ Time Frame: Day 1 to Day 4 ] [ Designated as safety issue: No ]
  • Part 2 : PK profile in plasma: determination of naproxen levels [ Time Frame: Day 1 to Day 4 ] [ Designated as safety issue: No ]
  • Part 2 : assess the general safety and tolerability [ Time Frame: Day 1 to Day 4 ] [ Designated as safety issue: Yes ]

Enrollment: 24
Study Start Date: January 2010
Study Completion Date: February 2010
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: naproxcinod 750 mg bid Drug: naproxcinod 750 bid
naproxcinod 750 bid
Experimental: naproxcinod 3000 mg od Drug: naproxcinod 3000 mg od
naproxcinod 3000 mg od
Active Comparator: naproxen 500 mg bid Drug: naproxen 500 mg bid
naproxen 500 mg bid

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:1.

  1. Healthy, non smoker male subjects aged 18 to 45 years (inclusive).
  2. Body Mass Index (BMI) between 18 and 30 kg/m² (inclusive) with body weight (BW) ≥ 50 kg.
  3. Normal physical examination (non clinically significant abnormalities), as judged by the investigator.
  4. Normal electrocardiogram (ECG) (12-lead), (non clinically significant abnormalities), as judged by the Investigator.
  5. 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).
  6. Supine Heart Rate (HR) between 45 and 90 bpm (inclusive).
  7. Oral body temperature (BT) between 36 and 37.5°C (inclusive).
  8. Subject must be able to understand the written information sheet and informed consent and comply with all study requirements.
  9. Subject must provide a written, dated and signed informed consent prior to any study procedure.

Exclusion Criteria:

  1. 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.
  2. 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.
  3. 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.
  4. Any clinically significant abnormal laboratory values, including creatinine clearance ≤ 80 mL/min as calculated with the Cockcroft-Gault formula.
  5. Seropositivity for HBs Ag, HCV Ab, HIV 1 or HIV 2 Ab.
  6. Any history of alcohol or drug abuse, or addiction within the last 2 years prior to enrollment.
  7. Positive drug screening (opiates, cannabinoids, cocaine, methadone, amphetamines, barbiturates, ecstasy).
  8. Positive alcohol or cotinine test.
  9. Donation of blood, plasma or platelets within 3 months prior to the Screening visit or donation planned during the 3 months following the study.
  10. Regular consumption of grapefruit juice or beverages containing xanthine bases (coffee, tea, cola: more than 5 cups or glasses a day).
  11. Current smokers or smoking history < 6 months.
  12. 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.
  13. 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).
  14. Use of antioxidant vitamin supplements within 1 week prior to enrollment.
  15. Use of mouthwash or toothpaste containing chlorhexidine within 1 week prior to randomization (applicable only for study Part 1).
  16. In custody due to an administrative or a legal decision, or under tutelage, or being admitted to a sanitary or social institution.
  17. Any direct or indirect involvement with the study conduct or staff at site or any family link with study site staff.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01404598

Sponsors and Collaborators
NicOx
Investigators
Principal Investigator: Antonio Rusca, MD FMH Cross Research S.A. Phase I Unit
  More Information

Additional Information:
No publications provided

Responsible Party: NicOx
ClinicalTrials.gov Identifier: NCT01404598     History of Changes
Other Study ID Numbers: HCT 3012-X-114
Study First Received: June 16, 2011
Last Updated: August 10, 2011
Health Authority: Switzerland: Swissmedic
United States: Food and Drug Administration

Additional relevant MeSH terms:
Naproxen
Naproxen-n-butyl nitrate
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Gout Suppressants
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents
Nitric Oxide Donors
Cardiovascular Agents

ClinicalTrials.gov processed this record on September 18, 2014