Safety and Pharmacokinetics Study of Intranasal Ketorolac in Elderly and Nonelderly Adult Healthy Subjects

A Phase 1 Safety and Pharmacokinetics Study of Intranasal Ketorolac in Elderly and Nonelderly Adult Healthy Subjects

This study had an open-label, single-dose design. All subjects received a single dose of 30 mg of intranasal ketorolac. Blood samples for determination of ketorolac plasma levels were obtained pre-dose and at specified time points over 24 hours post-dose.

The primary objective of this trial was to compare the pharmacokinetics of intranasal ketorolac between elderly and nonelderly adult subjects. The secondary objective was to evaluate the safety profile of intranasal ketorolac in elderly subjects.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects
• Intervention / Treatment: Drug: Ketorolac tromethamine

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33126
      • SeaView Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The elderly population consisted of male or female volunteers aged > of = 65 years
• The nonelderly adult population consisted of male or female volunteers aged < 65 years
• Generally good health in the opinion of the Investigator, as determined by a prestudy physical examination with no clinically significant abnormalities for age, vital signs within normal ranges or outside normal range but not deemed clinically significant for age in the opinion of the Investigator, and no clinically significant electrocardiogram (ECG) abnormalities for age
• Bilaterally patent nasal airways at screening as assessed by the Investigator
• Body mass index (BMI) 15-30 kg/m2
• Female subjects of childbearing potential must consent to use a medically acceptable method of contraception (oral or implanted contraceptive hormones, condom or diaphragm with spermicidal agent, intrauterine device, or surgical sterilization) throughout the study period
• Ability to provide written informed consent
• Prestudy clinical laboratory findings within normal ranges or if outside normal range not deemed clinically significant for age in the opinion of the Investigator

Exclusion Criteria:

• Allergy or sensitivity to ketorolac or formulation ingredients
• 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 interfere with the absorption of the nasal spray or with the assessment of AEs
• Use of any prescribed or over-the-counter (OTC) drug in the 72 h prior to entry into the study with the exception of occasional acetaminophen up to 24 h prior to entry
• Suspicion of rhinitis medicamentosa (chronic daily use of topical decongestants)
• Use of a monoamine oxidase (MAO) inhibitor in the 14 days prior to study entry
• Positive serum test for human immunodeficiency virus (HIV) or hepatitis B or C
• Positive alcohol breath test at screening or on entry into the study
• Positive urine screen for any nonprescribed drug of abuse at screening or on entry into the study
• History of cocaine use
• Blood donation within 30 days of beginning study participation
• Active peptic ulcer disease or a history of peptic ulcer disease or gastrointestinal bleeding
• Serum creatinine > 2.0 mg/dL
• Current tobacco use or a past history of smoking within 5 years of study entry
• Any other clinically significant medical problem, which in the opinion of the Investigator would interfere with study participation
• Participation within 30 days of study entry or within 5 times the half-life, whichever is longer, in another investigational drug study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Ketorolac tromethamine	Drug: Ketorolac tromethamine; Single dose of 30 mg of intranasal Ketorolac tromethamine (100 uL of a 15% solution in each nostril)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Cmax (Maximum Plasma Concentration)	Blood samples for PK analyses were obtained at pre-dose (15 minutes prior to ketorolac administration), 15 minutes, 30 minutes, 45 minutes, 1 hour, 1 hour and 30 minutes, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours and 24 hours post-dose
Tmax (Time to Reach Maximum Plasma Concentration)	Blood samples for PK analyses were obtained at pre-dose (15 minutes prior to ketorolac administration), 15 minutes, 30 minutes, 45 minutes, 1 hour, 1 hour and 30 minutes, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours and 24 hours post-dose
AUClast (Area Under the Plasma Concentration-time Profile From Time Zero to the Last Quantifiable Time Point Post-dose	Blood samples for PK analyses were obtained at pre-dose (15 minutes prior to ketorolac administration), 15 minutes, 30 minutes, 45 minutes, 1 hour, 1 hour and 30 minutes, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours and 24 hours post-dose
AUC (Area Under the Plasma Concentration-time Profile From Time 0 to Infinity	Blood samples for PK analyses were obtained at pre-dose (15 minutes prior to ketorolac administration), 15 minutes, 30 minutes, 45 minutes, 1 hour, 1 hour and 30 minutes, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours and 24 hours post-dose
t1/2z (Terminal Half-life)	Blood samples for PK analyses were obtained at pre-dose (15 minutes prior to ketorolac administration), 15 minutes, 30 minutes, 45 minutes, 1 hour, 1 hour and 30 minutes, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours and 24 hours post-dose
MRT (Mean Residence Time)	Blood samples for PK analyses were obtained at pre-dose (15 minutes prior to ketorolac administration), 15 minutes, 30 minutes, 45 minutes, 1 hour, 1 hour and 30 minutes, 2 hours, 4 hours, 6 hours, 8 hours, 12 hours, 15 hours and 24 hours post-dose

Collaborators and Investigators

• Sponsor: American Regent, Inc.
• Investigators: Study Chair: Lincoln Bynum, MD, ICON Developmental Solutions

Publications and helpful links

General Publications

• Bullingham R, Juan A. Comparison of intranasal ketorolac tromethamine pharmacokinetics in younger and older adults. Drugs Aging. 2012 Nov;29(11):899-904. doi: 10.1007/s40266-012-0023-2.

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (ACTUAL): April 1, 2008
• Study Completion (ACTUAL): July 1, 2008

Study Registration Dates

• First Submitted: June 1, 2011
• First Submitted That Met QC Criteria: June 1, 2011
• First Posted (ESTIMATE): June 3, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): February 6, 2013
• Last Update Submitted That Met QC Criteria: January 3, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Ketorolac; Ketorolac Tromethamine
• Other Study ID Numbers: ROX 2007-02