Lipidomics Screening of Celecoxib in ex Vivo Human Whole Blood Assay - Part B

• ClinicalTrials.gov Identifier: NCT02413203
• Recruitment Status: Completed
• First Posted: April 9, 2015
• Results First Posted: May 30, 2017
• Last Update Posted: May 30, 2017
• Sponsor: University of Pennsylvania
• Collaborator: Eli Lilly and Company
• Information provided by (Responsible Party): University of Pennsylvania

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Screening
• Condition: Healthy
• Interventions: Drug: Celecoxib; Drug: Placebo
• Enrollment: 20

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Celecoxib	Placebo
Arm/Group Description	Oral administration of a single pill of celecoxib (200 mg). Celecoxib pills will be over-encapsulated to match the placebo. Celecoxib: Blood and urine collections before and 3 hours after celecoxib administration.	Oral administration of a single placebo pill. Placebo: Blood and urine collections before and 3 hours after placebo administration.
Period Title: Overall Study
Started	10	10
Completed	10	10
Not Completed	0	0

Baseline Characteristics

Arm/Group Title		Celecoxib	Placebo	Total
Arm/Group Description		Oral administration of a single pill of celecoxib (200 mg). Celecoxib pills will be over-encapsulated to match the placebo. Celecoxib: Blood and urine collections before and 3 hours after celecoxib administration.	Oral administration of a single placebo pill. Placebo: Blood and urine collections before and 3 hours after placebo administration.	Total of all reporting groups
Overall Number of Baseline Participants		10	10	20
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	10 participants	10 participants	20 participants
		32.2 (8.6)	30 (9)	32.1 (8.6)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	10 participants	10 participants	20 participants
	Female	4 40.0%	3 30.0%	7 35.0%
	Male	6 60.0%	7 70.0%	13 65.0%

Outcome Measures

1. Primary Outcome

Title	Quantification of Plasma Lipids in the Whole Blood: Prostaglandin E2 (PGE2)
Description	PGE2 in blood taken from celecoxib-treated subjects and stimulated ex vivo with LPS was compared to similarly treated blood from placebo group. Plasma PGE2 was normalized to sample volume (ng/ml) and expressed as a percentage of subject’s pre-dose control using the formula: percentage of pre-dose control = (Cpost-dose/Cpre-dose) × 100%, where C represents PGE2 concentration in ng/ml.
Time Frame	A single visit of around 4 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Celecoxib	Placebo
Arm/Group Description:	Oral administration of a single pill of celecoxib (200 mg). Celecoxib pills will be over-encapsulated to match the placebo. Celecoxib: Blood and urine collections before and 3 hours after celecoxib administration.	Oral administration of a single placebo pill. Placebo: Blood and urine collections before and 3 hours after placebo administration.
Overall Number of Participants Analyzed	10	10
Mean (Standard Deviation); Unit of Measure: percentage of pre-dose control
	49.9 (26.59)	110 (49.2)

2. Primary Outcome

Title	Quantification of Plasma Lipids in the Whole Blood: Prostaglandin F2a (PGF2a)
Description	PGF2a in blood taken from celecoxib-treated subjects and stimulated ex vivo with LPS was compared to similarly treated blood from placebo group. Plasma PGF2a was normalized to sample volume (ng/ml) and expressed as a percentage of subject’s pre-dose control using the formula: percentage of pre-dose control = (Cpost-dose/Cpre-dose) × 100%, where C represents PGF2a concentration in ng/ml.
Time Frame	A single visit of around 4 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Celecoxib	Placebo
Arm/Group Description:	Oral administration of a single pill of celecoxib (200 mg). Celecoxib pills will be over-encapsulated to match the placebo. Celecoxib: Blood and urine collections before and 3 hours after celecoxib administration.	Oral administration of a single placebo pill. Placebo: Blood and urine collections before and 3 hours after placebo administration.
Overall Number of Participants Analyzed	10	10
Mean (Standard Deviation); Unit of Measure: percentage of pre-dose control
	45.48 (20.51)	97.2 (32.9)

3. Primary Outcome

Title	Quantification of Plasma Lipids in the Whole Blood: Thromboxane B2 (TxB2)
Description	TxB2 in blood taken from celecoxib-treated subjects and stimulated ex vivo with LPS was compared to similarly treated blood from placebo group. Plasma TxB2 was normalized to sample volume (ng/ml) and expressed as a percentage of subject’s pre-dose control using the formula: percentage of pre-dose control = (Cpost-dose/Cpre-dose) × 100%, where C represents TxB2 concentration in ng/ml.
Time Frame	A single visit of around 4 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Celecoxib	Placebo
Arm/Group Description:	Oral administration of a single pill of celecoxib (200 mg). Celecoxib pills will be over-encapsulated to match the placebo. Celecoxib: Blood and urine collections before and 3 hours after celecoxib administration.	Oral administration of a single placebo pill. Placebo: Blood and urine collections before and 3 hours after placebo administration.
Overall Number of Participants Analyzed	10	10
Mean (Standard Deviation); Unit of Measure: percentage of pre-dose control
	52.2 (16.9)	83.4 (12.8)

4. Primary Outcome

Title	Quantification of Plasma Lipids in the Whole Blood: 15-Hydroxyeicosatetraenoic Acid (15-HETE)
Description	15-HETE in blood taken from celecoxib-treated subjects and stimulated ex vivo with LPS was compared to similarly treated blood from placebo group. Plasma 15-HETE was normalized to sample volume (ng/ml) and expressed as a percentage of subject’s pre-dose control using the formula: percentage of pre-dose control = (Cpost-dose/Cpre-dose) × 100%, where C represents 15-HETE concentration in ng/ml.
Time Frame	A single visit of around 4 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Celecoxib	Placebo
Arm/Group Description:	Oral administration of a single pill of celecoxib (200 mg). Celecoxib pills will be over-encapsulated to match the placebo. Celecoxib: Blood and urine collections before and 3 hours after celecoxib administration.	Oral administration of a single placebo pill. Placebo: Blood and urine collections before and 3 hours after placebo administration.
Overall Number of Participants Analyzed	10	10
Mean (Standard Deviation); Unit of Measure: percentage of pre-dose control
	49 (18.7)	81.65 (22.8)

5. Secondary Outcome

Title	Urinary Lipid Metabolites: PGE2 Metabolite (PGE-M)
Description	Effect of celecoxib on systemic PGE2 was assessed by comparing urine PGE-M in celecoxib vs placebo-treated groups. Urine data are reported as a percentage of the volunteer’s own pre-dose control using the formula: percentage of pre-dose control = (Cpost-dose/Cpre-dose) × 100%, where C represents metabolite concentration in ng/mg creatinine.
Time Frame	A single visit of around 4 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Celecoxib	Placebo
Arm/Group Description:	Oral administration of a single pill of celecoxib (200 mg). Celecoxib pills will be over-encapsulated to match the placebo. Celecoxib: Blood and urine collections before and 3 hours after celecoxib administration.	Oral administration of a single placebo pill. Placebo: Blood and urine collections before and 3 hours after placebo administration.
Overall Number of Participants Analyzed	10	10
Mean (Standard Deviation); Unit of Measure: percentage of pre-dose control
	79.15 (24.19)	106 (20.1)

6. Secondary Outcome

Title	Celecoxib Plasma Concentration
Description	Celecoxib plasma concentration will be measured in drug-treated and placebo groups by UPLC-MS/MS, and will be expressed as amount of the drug per volume of plasma (ng/ml). At Tmax of 3 hours after a single oral dose of celecoxib of 200 mg, drug plasma concentration should correspond to the maximum plasma concentration or Cmax.
Time Frame	A single visit of around 4 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Celecoxib	Placebo
Arm/Group Description:	Oral administration of a single pill of celecoxib (200 mg). Celecoxib pills will be over-encapsulated to match the placebo. Celecoxib: Blood and urine collections before and 3 hours after celecoxib administration.	Oral administration of a single placebo pill. Placebo: Blood and urine collections before and 3 hours after placebo administration.
Overall Number of Participants Analyzed	10	10
Mean (Standard Deviation); Unit of Measure: ng/ml
	352.6 (221)	0 (0)

7. Secondary Outcome

Title	Urinary Lipid Metabolites: PGI2 Metabolite (PGI-M)
Description	Effect of celecoxib on systemic PGI2 was assessed by comparing urine PGI-M in celecoxib vs placebo-treated groups. Urine data are reported as a percentage of the volunteer’s own pre-dose control using the formula: percentage of pre-dose control = (Cpost-dose/Cpre-dose) × 100%, where C represents metabolite concentration in ng/mg creatinine.
Time Frame	A single visit of around 4 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Celecoxib	Placebo
Arm/Group Description:	Oral administration of a single pill of celecoxib (200 mg). Celecoxib pills will be over-encapsulated to match the placebo. Celecoxib: Blood and urine collections before and 3 hours after celecoxib administration.	Oral administration of a single placebo pill. Placebo: Blood and urine collections before and 3 hours after placebo administration.
Overall Number of Participants Analyzed	10	10
Mean (Standard Deviation); Unit of Measure: percentage of pre-dose control
	41.47 (11)	78.6 (52.23)

8. Secondary Outcome

Title	Urinary Lipid Metabolites: TxB2 Metabolite (Tx-M)
Description	Effect of celecoxib on systemic TxB2 was assessed by comparing urine Tx-M in celecoxib vs placebo-treated groups. Urine data are reported as a percentage of the volunteer’s own pre-dose control using the formula: percentage of pre-dose control = (Cpost-dose/Cpre-dose) × 100%, where C represents metabolite concentration in ng/mg creatinine.
Time Frame	A single visit of around 4 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Celecoxib	Placebo
Arm/Group Description:	Oral administration of a single pill of celecoxib (200 mg). Celecoxib pills will be over-encapsulated to match the placebo. Celecoxib: Blood and urine collections before and 3 hours after celecoxib administration.	Oral administration of a single placebo pill. Placebo: Blood and urine collections before and 3 hours after placebo administration.
Overall Number of Participants Analyzed	10	10
Mean (Standard Deviation); Unit of Measure: percentage of pre-dose control
	79 (14.4)	77.9 (17.2)

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Celecoxib	Placebo
Arm/Group Description	Oral administration of a single pill of celecoxib (200 mg). Celecoxib pills will be over-encapsulated to match the placebo. Celecoxib: Blood and urine collections before and 3 hours after celecoxib administration.	Oral administration of a single placebo pill. Placebo: Blood and urine collections before and 3 hours after placebo administration.
All-Cause Mortality
	Celecoxib	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/10 (0.00%)	0/10 (0.00%)
Serious Adverse Events
	Celecoxib	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/10 (0.00%)	0/10 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Celecoxib	Placebo
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/10 (0.00%)	0/10 (0.00%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Garret A. FitzGerald
• Organization: Univesrity of Pennsylvania
• Phone: 215-898-1185
• EMail: garret@upenn.edu

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT02413203 History of Changes
• Other Study ID Numbers: 818658-Part B
• First Submitted: March 19, 2015
• First Posted: April 9, 2015
• Results First Submitted: March 6, 2017
• Results First Posted: May 30, 2017
• Last Update Posted: May 30, 2017