Tolerability, Safety and Pharmacokinetics of Four Formulations of Ketorolac Tromethamine in Healthy Volunteers

NCT01355588 | Completed Phase 1 Results

• 1 other identifier: ROX 2005-02
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This was a phase 1, double-blind, 4-way crossover study in healthy male and female volunteers. Subjects received 4 formulations of intranasal ketorolac tromethamine 30 mg. There was a wash-out period of 3-7 days between each dose. On Day 1 of each period subjects were randomised to receive either a single intranasal dose of 30 mg ketorolac tromethamine alone or single intranasal dose of 30 mg ketorolac tromethamine with 4%, 5% or 6% lidocaine hydrochloride. At the end of the study each subject had received all 4 treatments. The primary objective of this study in healthy volunteers was to compare the safety, tolerability, and pharmacokinetics of 4 formulations of ketorolac tromethamine. A secondary objective was to monitor lidocaine hydrochloride plasma levels.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (3)

• Maximum Observed Plasma Concentration (Cmax)

  Anytime at pre-dose, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours (ketorolac tromethamine only), and 24 hours (ketorolac tromethamine only) post-dose

• Area Under the Plasma Concentration-time Profile From Time Zero to the Last Quantifiable Post-dose (AUC 0-t)

  Anytime at pre-dose, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours (ketorolac tromethamine only), and 24 hours (ketorolac tromethamine only) post-dose

• Area Under the Plasma Concentration-time Profile From Time Zero to Infinity (AUC 0-∞)

  Anytime at pre-dose, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours (ketorolac tromethamine only), and 24 hours (ketorolac tromethamine only) post-dose

Secondary Outcomes (1)

• Time to Reach Maximum Plasma Concentration (Tmax)

  Anytime at pre-dose, 15 minutes, 30 minutes, 45 minutes, 1 hour, 1.5 hours, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours (ketorolac tromethamine only), and 24 hours (ketorolac tromethamine only) post-dose

Study Arms (4)

Ketorolac Tromethamine

EXPERIMENTAL

Drug: Ketorolac Tromethamine

Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl)

EXPERIMENTAL

Drug: Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl)

Ketorolac Tromethamine with 5% Lidocaine HCl

EXPERIMENTAL

Drug: Ketorolac Tromethamine with 5% Lidocaine HCl

Ketorolac Tromethamine with 6% Lidocaine HCl

EXPERIMENTAL

Drug: 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl

Interventions

Ketorolac Tromethamine DRUG

30 mg Ketorolac Tromethamine intranasal (IN)

Ketorolac Tromethamine

Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl) DRUG

30 mg Ketorolac Tromethamine with 4% Lidocaine HCl IN

Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl)

Ketorolac Tromethamine with 5% Lidocaine HCl DRUG

30 mg Ketorolac Tromethamine with 5% Lidocaine HCl IN

Ketorolac Tromethamine with 5% Lidocaine HCl

30 mg Ketorolac Tromethamine with 6% Lidocaine HCl DRUG

30 mg Ketorolac Tromethamine with 6% Lidocaine HCl IN

Ketorolac Tromethamine with 6% Lidocaine HCl

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female volunteers, aged 18 to 60 years inclusive
• Female subjects of child bearing potential must have had a negative urine pregnancy test prior to entry into the study and must not have been breast feeding
• All female subjects of child bearing potential and all male subjects with female partners of child bearing potential must have consented to use a medically acceptable method of contraception (oral or implanted contraceptive hormones, condom or diaphragm with spermicidal agent, intrauterine device or surgical sterilisation) throughout the study period
• Subject had given signed informed consent
• Subject was within 20% of normal weight for his/her height and body build according to the table of "Desirable Weights for Men and Women" (Metropolitan Life Insurance Co. 1999)
• Subject's medical history was considered normal, with no clinically significant abnormalities
• Subject was considered to be in good health in the opinion of the Investigator as determined by a pre-study physical examination with no clinically significant abnormalities, vital signs within normal range and an ECG with no clinically significant abnormalities
• Subject's pre-study clinical laboratory findings were within normal range or, if outside of the normal range, not deemed clinically significant in the opinion of the Investigator
• Subject had bilateral patent nasal airways at screening as assessed by the Investigator
• Body weight was at least 70 kg

You may not qualify if:

• Subject had a clinically significant illness in the 4 weeks before screening
• Use of prescribed medications in the 3 weeks prior to dosing or over-the-counter preparations for 7 days prior to dosing, except paracetamol which was allowed up to 48 hours prior to dosing. However, use of multivitamins and oral contraceptives were permitted
• Subject had a significant history of drug/solvent abuse, or a positive drugs of abuse test at screening
• Subject had history of alcohol abuse or drank in excess of 28 units per week (males) or 21 units per week (females)
• Current tobacco use or a history of smoking within the past 5 years
• Subject was, in the opinion of the Investigator, not suitable to participate in the study
• Subjects who had participated in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing
• Subjects who had a positive result of HIV screen, Hepatitis B screen or Hepatitis C screen
• Subjects with a serious adverse reaction or significant hypersensitivity to any drug
• Subjects who has donated 500 mL or more of blood within the 3 months prior to screening
• Any history of co-existing nasal polyps, NSAID sensitivity and asthma
• Allergic reaction to aspirin or other NSAIDs
• Current upper respiratory tract infection or other respiratory tract condition that could have interfered with the absorption of the nasal spray or with the assessment of AEs
• Any suspicion of rhinitis medicamentosa (chronic daily use of topical decongestants)
• Use of a monoamine oxidase inhibitor in the 14 days prior to study entry

Sponsors & Collaborators

• Egalet Ltd: lead

Study Sites (1)

Medeval Ltd

Manchester, United Kingdom

Location

MeSH Terms

Interventions

Ketorolac Tromethamine; Lidocaine

Intervention Hierarchy (Ancestors)

Indomethacin; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines

Results Point of Contact

• Title: David Bregman, M.D., Ph.D.
• Organization: Luitpold Pharmaceuticals, Inc.

dbregman@lpicrd.com

610-650-4200

Study Officials

• Cyril Clarke, BSc MB BS MFPM

  Medeval Limited

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: May 16, 2011
• First Posted: May 18, 2011
• Study Start: August 1, 2005
• Primary Completion: September 1, 2005
• Study Completion: March 1, 2006
• Last Updated: March 16, 2017
• Results First Posted: May 3, 2013

Record last verified: 2017-02

Locations

GB (1)