Variability in Response to Non-steroidal Anti-inflammatory Drugs

NCT02502006 | Terminated Phase 1 Results

• 2 other identifiers: 8207155U54HL117798
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This research study will evaluate inter-individual variability in the response to the non-steroidal anti-inflammatory drugs (NSAIDs), celecoxib and naproxen, among healthy adults. It will also investigate what factors, like age, sex, or genetic background, cause this variability.

Conditions

Healthy

Keywords

Non-steroidal Anti-inflammatory Drugs; Healthy volunteers; Celecoxib; Naproxen; Prostaglandin; Cyclooxygenase

Outcome Measures

Primary Outcomes (4)

• COX-1 Activity ex Vivo

  COX-1 activity was measured ex vivo using a whole blood assay. Thromboxane A2 serum concentrations were quantified before, and 0.5, 1, 2, 4, 8, and 12 h after treatment and expressed as AUC over the 12 hour dosing interval.

  12 hours

• COX-2 Activity ex Vivo

  COX-2 activity was assessed ex vivo using a whole blood assay. Prostaglandin E2 concentrations in LPS-treated plasma were quantified before, and 0.5, 1, 2, 4, 8, and 12 h after treatment and expressed as AUC over the 12 hour dosing interval.

  12 hours

• COX-1 Activity in Vivo

  COX-1 activity was measured in vivo by quantifying the urinary metabolite of thromboxane A2 before, and 1, 2, 4, 8, and 12 h after treatment, normalized to urinary creatinine and expressed as AUC over the 12 hour dosing interval.

  12 hours

• COX-2 Activity in Vivo

  COX-2 activity was measured in vivo by quantifying the urinary metabolite of prostaglandin I2 before, and 1, 2, 4, 8, and 12 h after treatment, normalized to urinary creatinine and expressed as AUC over the 12 hour dosing interval.

  12 hours

Secondary Outcomes (3)

• Systolic Blood Pressure

  12 hours

• Diastolic Blood Pressure

  12 hours

• Mean Arterial Pressure

  12 hours

Study Arms (2)

High Dose

EXPERIMENTAL

During each treatment phase, subjects will receive celecoxib (200 mg by mouth twice daily), naproxen (500 mg by mouth twice daily), or placebo (twice daily) for 7 days. Subjects will be instructed to take the study medications twice a day (at approximately 8 AM and 8 PM) on an empty stomach with a full glass of water.

Drug: Celecoxib; Drug: Naproxen; Drug: Placebo

Low dose

EXPERIMENTAL

During each treatment phase, subjects will receive celecoxib (100 mg by mouth twice daily), naproxen (250 mg by mouth twice daily), or placebo (twice daily) for 7 days. Subjects will be instructed to take the study medications twice a day (at approximately 8 AM and 8 PM) on an empty stomach with a full glass of water.

Drug: Celecoxib; Drug: Naproxen; Drug: Placebo

Interventions

Celecoxib DRUG

Also known as: Celebrex

High Dose; Low dose

Naproxen DRUG

Also known as: Naprosyn

High Dose; Low dose

Placebo DRUG

High Dose; Low dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult men and women greater than 18 years of age who are non-smokers and in good health based on medical history, physical examination, vital signs, and laboratory tests. Volunteers with adequately controlled hypertension and hyperlipidemia (total cholesterol of ≤270 mg/dL) may participate in the study.

You may not qualify if:

• Female subjects who are pregnant or nursing a child.
• Subjects who have received an investigational drug or used an experimental medical device within 30 days prior to screening, or who gave a blood donation of ≥ one pint within 8 weeks prior to screening.
• Subjects with any coagulation, bleeding or blood disorders.
• Subjects who are sensitive or allergic to celecoxib (Celebrex) or naproxen (Naprosyn) or their components.
• Subjects who are sensitive or allergic to aspirin or other NSAIDs.
• Subjects with documented history of any gastrointestinal disorders, including bleeding ulcers.
• History of significant cardiovascular disease (including stroke or TIA), renal, hepatic, respiratory (except infections which longer \> 6 months prior to screening), immune, endocrine, hematopoietic disorder or neurological disorders.
• History of cancer within the last 5 years (except for cutaneous basal cell or squamous cell cancer resolved by excision, or carcinoma in situ of the cervix adequately treated).
• Has taken NSAIDs or anti-secretory agents (proton pump inhibitors or H2 receptor antagonists) within 14 days prior to study drug administration
• Has ever taken the any anti-platelet or anti-coagulant agents
• Used dietary or herbal supplements containing salicylates, Vitamin E, fish oil, or any other herbal supplements, within 14 days of study drug administration.
• Subjects with any abnormal laboratory value or physical finding that according to the investigator may interfere with interpretation of the study results, be indicative of an underlying disease state, or compromise the safety of a potential subject.
• Subjects who have had a history of drug or alcohol abuse within the last 6 months.
• Subjects who are unwilling to provide a blood sample for genetic analyses and creation of a lymphoblastoid cell line.

Sponsors & Collaborators

• University of Pennsylvania: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Institute for Translational Medicine and Therapeutics (ITMAT), University of Pennsylvania School of Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (2)

• Theken KN, Ghosh S, Skarke C, Fries S, Lahens NF, Sarantopoulou D, Grant GR, FitzGerald GA, Grosser T. Degree of Cyclooxygenase-2 Inhibition Modulates Blood Pressure Response. Hypertension. 2026 Feb;83(2):e25516. doi: 10.1161/HYPERTENSIONAHA.124.25516. Epub 2025 Dec 29.

  PMID: 41459594 DERIVED

• Theken KN, Ghosh S, Skarke C, Fries S, Lahens NF, Sarantopoulou D, Grant GR, FitzGerald GA, Grosser T. Degree of Cyclooxygenase-2 Inhibition Modulates Blood Pressure Response to Celecoxib and Naproxen. medRxiv [Preprint]. 2024 May 31:2024.05.30.24308244. doi: 10.1101/2024.05.30.24308244.

  PMID: 38854091 DERIVED

MeSH Terms

Interventions

Celecoxib; Naproxen

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Naphthaleneacetic Acids; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Katherine N. Theken, PharmD, PhD
• Organization: University of Pennsylvania

ktheken@upenn.edu

2158987470

Study Officials

• Garret A FitzGerald, MD

  University of Pennsylvania, Institute for Translational Medicine and Therapeutics

  PRINCIPAL INVESTIGATOR

• Tilo Grosser, MD

  University of Pennsylvania, Institute for Translational Medicine and Therapeutics

  PRINCIPAL INVESTIGATOR

• Katherine N Theken, PharmD, PhD

  University of Pennsylvania, Institute for Translational Medicine and Therapeutics

  PRINCIPAL INVESTIGATOR

• Carsten Skarke, MD

  University of Pennsylvania, Institute for Translational Medicine and Therapeutics

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 16, 2015
• First Posted: July 17, 2015
• Study Start: November 1, 2015
• Primary Completion: September 1, 2022
• Study Completion: September 1, 2022
• Last Updated: December 13, 2023
• Results First Posted: December 13, 2023

Record last verified: 2023-11

Locations

US (1)