Completed

NCT Number: NCT01363089

Study to Assess the PK of Ketorolac Tromethamine Intranasal and to Assess the Effects of a Oxymetazoline Hydrochloride on the PK of Ketorolac Tromethamine

This was an open label, two way crossover study in healthy male subjects. Two treatments were administered to each subject, one treatment per study period, in a randomized manner. Subjects remained resident in the Clinical Unit from the evening of Day 1 until the morning of Day 2 of each period and there was a washout period of at least 2 days between treatments. A post study medical examination was performed prior to discharge in Period 2.

The objective of this study was to assess the effects of a single dose of intranasal oxymetazoline hydrochloride on the pharmacokinetics of intranasal ketorolac in healthy male subjects.

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Key information

Conditions

Assess Pharmacokinetics of Ketorolac Tromethamine Intranasal and Assess Effects of a Oxymetazoline Hydrochloride on the PK of Ketorolac Tromethamine

Age range

18 year–62 year

Sex eligibility

Male

Study type

Interventional

Phase

Phase 1

Primary location

ICON Development Solutions

Manchester, United Kingdom

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

Subject was male and aged 18 to 62 years inclusive
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, intrauterine device or surgical sterilization plus condom or diaphragm with spermicidal agent) throughout the study period
Subject had given signed informed consent
Subject was within 20% of normal weight for his 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 ranges and an electrocardiogram (ECG) with no clinically significant abnormalities
Subject's pre-study clinical laboratory findings were within normal range or if outside of the normal range were not deemed clinically significant in the opinion of the Investigator
Subject had bilateral patent nasal airways at screening and Day 1 as assessed by the Investigator
Subject had a body weight of at least 60 kg

Exclusion criteria

Subject had had a clinically significant illness in the 4 weeks before screening
Subject used 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 (h) prior to dosing. Use of multivitamins was permitted
Subject had a significant history of drug/solvent abuse, or a positive drugs of abuse test at screening
Subject had a history of alcohol abuse or currently drank in excess of 28 units per week
Subject currently used tobacco or had a history of smoking within the past 5 years
Subject was in the opinion of the Investigator not suitable to participate in the study
Subject had participated in any clinical study with an investigational drug/device within 3 months prior to dosing
Subject had a positive human immunodeficiency virus (HIV), hepatitis B or hepatitis C screen
Subject had had a serious adverse reaction or significant hypersensitivity to any drug
Subject had donated 500 mL or more of blood within the 3 months prior to screening
Subject had any history of co-existing nasal polyps, NSAID sensitivity and asthma
Subject had an allergic reaction to aspirin or other NSAIDs
Subject currently had an upper respiratory tract infection or other respiratory tract condition that could interfere with the absorption of the nasal spray or with the assessment of AEs
Subject had any suspicion of rhinitis medicamentosa (chronic daily use of topical decongestants)
Subject had used a monoamine oxidase inhibitor in the 14 days prior to study entry
Subject had an active peptic ulcer disease, gastrointestinal bleeding or perforation, or a history of peptic ulcer disease or gastrointestinal bleeding
Subject had anemia due to unexplained or known gastrointestinal bleeding
Subject had a history of asthma or any other chronic pulmonary disorder
Subject had renal impairment or a risk of renal failure due to volume depletion
Subject had a previous history of nasal surgery

Treatment and study plan

Ketorolac Tromethamine

Drug

30 mg of intranasal ketorolac tromethamine (one 100 µL spray into each nostril of a 15%, pH 7.2 solution)

Oxymetazoline Hydrochloride

Drug

Single intranasal dose of oxymetazoline hydrochloride (Afrazine®) (3 sprays of a 0.05% solution into each nostril) followed 30 minutes later by 30 mg of intranasal ketorolac tromethamine (one 100 µL spray into each nostril of a 15%, pH 7.2 solution)

Primary outcomes

Cmax (the maximum observed plasma concentration)

Time frame: All PK parameters were assessed using blood samples collected pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose

Pharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each treatment, together with the individual plasma concentrations of ketorolac.
Tmax (the time to maximum concentration)

Time frame: All PK parameters were assessed using blood samples collected pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose

Pharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each treatment, together with the individual plasma concentrations of ketorolac.
AUC 0-t (the area under the plasma concentration-time curve (AUC) from time zero to the last quantifiable time point post-dose

Time frame: All PK parameters were assessed using blood samples collected pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose

Pharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each treatment, together with the individual plasma concentrations of ketorolac.
AUCinf (the AUC from time zero to infinity, where possible

Time frame: All PK parameters were assessed using blood samples collected pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose

Pharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each treatment, together with the individual plasma concentrations of ketorolac.
t1/2z (the terminal half-life, where possible

Time frame: All PK parameters were assessed using blood samples collected pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose

Pharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each treatment, together with the individual plasma concentrations of ketorolac.
MRT (the mean residence time)

Time frame: All PK parameters were assessed using blood samples collected pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose

Pharmacokinetic analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times for ketorolac assay were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each treatment, together with the individual plasma concentrations of ketorolac.

Sponsors and collaborators

Lead sponsor

Egalet Ltd

Industry

Registry information

Official study title

Open Label, 2-Way Crossover Study to Assess the PK of Intranasal Ketorolac Tromethamine and to Assess the Effects of a Single Dose of Oxymetazoline Hydrochloride on the PK of Intranasal Ketorolac Tromethamine in Healthy Male Subjects

Important dates

Study start: 2007
Primary completion: 2007
Study completion: 2008
First posted: Jun 1, 2011
Registry last updated: Feb 9, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.