A Study of LY3023703 Testing Pain Relief After Wisdom Teeth Removal

• ClinicalTrials.gov Identifier: NCT01872910
• Recruitment Status: Completed
• First Posted: June 7, 2013
• Results First Posted: December 14, 2017
• Last Update Posted: September 23, 2019
• Sponsor: Eli Lilly and Company
• Information provided by (Responsible Party): Eli Lilly and Company

Study Description

Brief Summary:

The main purpose of this study is to test if a single dose of LY3023703 relieves pain after wisdom teeth removal. The study will last about one week for each participant, not including screening.

Condition or disease	Intervention/treatment	Phase
Acute Pain	Drug: Placebo; Drug: LY3023703; Drug: Celecoxib	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 124 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Evaluation of the Acute Analgesic Efficacy of a Single Dose of LY3023703 in Patients With Postsurgical Dental Pain: A Parallel, Double-Blind, Randomized, Placebo and Positive Control Study
• Study Start Date: June 2013
• Actual Primary Completion Date: October 2013
• Actual Study Completion Date: October 2013

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo; Part A: Single oral administration of placebo matching corresponding LY3023703 dose administered orally once as a capsule post dental surgery. Part B: Single oral administration of placebo matching corresponding LY3023703 administered orally once as a capsule, post dental surgery and post dialysate probe placement. Part B of this study assessed whether LY3023703 selectively inhibited the prostaglandin E(PGE) surge in the wound dialysate during the postoperative period.	Drug: Placebo; Administered orally
Experimental: 30 milligrams (mg) LY3023703; Part A: Single oral administration of 30 milligrams (mg) LY3023703 administered orally once as a 30-milligrams (mg) capsule post dental surgery. Part B: Single oral administration of 30 milligrams (mg) LY3023703 administered orally once as a 30-mg capsule, post dental surgery and post dialysate probe placement. Part B of this study assessed whether LY3023703 selectively inhibited the prostaglandin E(PGE) surge in the wound dialysate during the postoperative period.	Drug: LY3023703; Administered orally; Other Name: LY3023703 phosphate
Active Comparator: 400 mg Celecoxib; Part A: Single oral administration of 400 mg celecoxib (Positive control) administered orally once as two 200-mg capsules post dental surgery (Positive control). Participants received two 200-mg celecoxib capsules during Pre-Part B.The purpose of Pre-Part B was to develop proficiency in the dialysate placement, collection, and maintenance techniques before moving to Part B. Celecoxib was not administered in Part B. Part B of this study assessed whether LY3023703 selectively inhibited the prostaglandin E(PGE) surge in the wound dialysate during the postoperative period.	Drug: Celecoxib; Administered orally

Outcome Measures

Primary Outcome Measures :

1. Part A: Weighted Mean Change From Baseline in Pain Intensity Over the First 8 Hours Post-Dose Using VAS [ Time Frame: 0 to 8 h post-dose ]
   Pain intensity was rated by the participant on a 100-mm VAS: 0 mm (no pain) and 100 mm (worst pain imaginable). The participant marked the line at the point that corresponded with his or her perception of pain. Weighted mean change from baseline was calculated as: [the area under the change in pain intensity versus time curve] / 8 hours (h). The baseline pain intensity was the pain assessment prior to dosing of study medication (0 h). Least Squares (LS) mean were calculated using a Bayesian analysis of covariance analysis (ANCOVA) adjusted for treatment as a fixed effect and baseline pain VAS as a continuous covariate. The measure of dispersion reported is 95% Credible Interval (CrI) not Confidence Interval (CI). A negative direction indicates a pain reduction from baseline.

Secondary Outcome Measures :

1. Total Pain Relief (TOPAR) Score at 4, 6, 8, 12 and 24 Hours Post-Dose [ Time Frame: 0 to 4, 0 to 6, 0 to 8, 0 to 12, and 0 to 24 h post-dose ]

   TOPAR was calculated as the area under the pain relief versus time curve of the participant reported pain relief scores from the 5-point pain relief scale of 0 (no pain relief) to 4 (complete pain relief). LS mean were calculated using ANCOVA adjusted for treatment as a fixed effect. The measure of dispersion reported is CrI not CI. A negative direction indicated a pain relief from baseline.

   Pre-Part B used 3 participants in order for the study site to develop proficiency in the dialysate placement, collection, and maintenance techniques. There were no planned efficacy analysis for Pre-Part B per protocol.

2. Weighted Mean Change From Baseline in Pain Intensity Over the First 24 Hours Post-Dose as Measured by VAS [ Time Frame: Part A and B: 0 to 4, 0 to 6, 0 to 12, and 0 to 24 h post-dose and Part B 0 to 8 h post-dose ]

   Pain intensity was rated by the participant on a 100-mm VAS: 0 mm (no pain) and 100 mm (worst pain imaginable). The participant marked the line at the point that corresponded with his or her perception of post oral surgery pain. Weighted mean change from baseline was calculated as: [area under the change in pain intensity versus time curve] / [time period that is (i.e.) 24 h for 0 to 24 h endpoint]. The baseline pain intensity was the pain assessment prior to dosing of study medication. LS mean were calculated using ANCOVA adjusted for treatment, time and interaction of treatment as a fixed effect and baseline pain VAS as a continuous covariate. The measure of dispersion reported is the 95% CrI not CI. A negative direction indicated a pain reduction from baseline.

   Pre-Part B used 3 participants in order for the study site to develop proficiency in the dialysate placement, collection, and maintenance techniques. There were no planned efficacy analysis for Pre-Part B per protocol.

3. Summed Pain Intensity Difference (SPID) Over the First 24 Hours Post-Dose as Measured by a 4-point Categorical Scale [ Time Frame: 0 to 4, 0 to 6, 0 to 8, 0 to 12, and 0 to 24 h post-dose ]

   The summed (time-weighted) pain intensity difference to baseline (SPID) at 4, 6, 8, 12, and 24 h post-dosing, as measured by a participant-rated 4-point categorical scale of 0 (no pain) to 3 (severe pain) and was calculated as: the area under the change in pain intensity versus time curve. Total scores range: -24 (best) to 8 (worst) for SPID 0 to 8 h. Score ranges for SPID(0-4h), SPID(0-6), SPID(0-12) and SPID(0-24) are -12 to 4, -18 to 6, -36 to 12 and -72 to 24 respectively. Participants were required to have moderate (score=2) or severe (score=3) pain at baseline in order to be eligible for randomization.LS mean were calculated using ANCOVA and was adjusted for treatment as a fixed effect and baseline pain intensity as a continuous covariate. The measure of dispersion reported is 95% CrI not CI. A negative direction indicated a pain reduction from baseline.

   There were no planned efficacy analysis for Pre-Part B per protocol.

4. Time to First Use of Rescue Medication [ Time Frame: Study drug administration to first use of rescue medication (0 to 24 h post-dose) ]

   Time to first use of rescue medication is defined as the time from study drug administration to the measured first use of rescue medication in hours. Participants were censored at 24 h post-dose if no rescue medication was administered.

   Pre-Part B used 3 participants in order for the study site to develop proficiency in the dialysate placement, collection, and maintenance techniques. There were no planned efficacy analysis for Pre-Part B per protocol.

5. Part A: Time to Onset of First Perceptible Pain Relief [ Time Frame: Study drug administration to first perceptible pain relief (0 to 24 h post-dose) ]
   Time to onset of the first perceptible pain relief is defined as the time from study drug administration to the measured onset of first perceptible pain relief in hours as reported by the participant. Participants who received rescue mediation prior to first perceptible pain relief were censored at the time the rescue medication was received.
6. Part A: Time to Onset of Meaningful Pain Relief [ Time Frame: Study drug administration to meaningful pain relief (0 to 24 h post-dose) ]
   Time to onset of meaningful pain relief is defined as the time from study drug administration to the measured onset of meaningful pain relief in hours as reported by the participant. Participants who received rescue mediation prior to meaningful pain relief were censored at the time the rescue medication was received.
7. Part A: Patient Global Impression of Improvement (PGI-I) Scale Score [ Time Frame: 2, 4, 8, 12 and 24 h post-dose ]
   PGI-I is a participant-rated instrument that measures the improvement of the participants symptoms on a 7-point scale: 1 (very much improved), 4 (no change), and 7 (very much worse). LS mean was calculated using Mixed Effect Model Repeated Measures (MMRM) adjusted for treatment, time, the interaction of treatment and time and baseline pain VAS and fixed effects.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Have at least 2 third molars which are clinically indicated for extraction. At least 1 molar should be a mandibular third molar with partial or complete bony impaction
• Are overtly healthy as determined by medical history and limited physical examination

Exclusion Criteria:

• Have chronic pain [for example (e.g.), fibromyalgia] or are experiencing episodic pain not related to the wisdom teeth (e.g., migraine pain) that could affect pain measurements as judged by the investigator
• Have temporomandibular joint disease or other condition which could affect pain processing or sensation, affect recovery from dental surgery, or otherwise affect ability to assess pain signal, in the opinion of the investigator
• Have substantial anxiety regarding dental or medical procedures as measured by the Corah Dental Anxiety Scale
• Are currently using or have recently used drugs that may confound assessment of the inflammatory response or pain including, but not limited to, nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin and other analgesics, antihistamines, steroids, antidepressants, attention-enhancing drugs, or herbal supplements

Contacts and Locations

Locations

United States, Texas

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Austin, Texas, United States, 78705

Sponsors and Collaborators

Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

More Information

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01872910
• Other Study ID Numbers: 14852; I6H-MC-MCBC ( Other Identifier: Eli Lilly and Company )
• First Posted: June 7, 2013
• Results First Posted: December 14, 2017
• Last Update Posted: September 23, 2019
• Last Verified: September 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)
• Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• URL: https://vivli.org/

Keywords provided by Eli Lilly and Company:

Wisdom tooth extraction

Additional relevant MeSH terms:

Acute Pain; Pain; Neurologic Manifestations; Celecoxib; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action