A Phase 1, Double-blind, 4-way Crossover Study of the Tolerability, Safety and Pharmacokinetics of 4 Formulations of Ketorolac Tromethamine by Intranasal Administration in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Egalet Ltd
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Maximum Observed Plasma Concentration (Cmax)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
- •Active peptic ulcer disease, gastrointestinal bleeding or perforation, or a history of peptic ulcer disease or gastrointestinal bleeding
- •Anemia due to unexplained or known gastrointestinal bleeding
- •History of asthma or any other chronic pulmonary disorder
- •Renal impairment or a risk of renal failure due to volume depletion
- •Known sensitivity to lidocaine hydrochloride
研究组 & 干预措施
Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl)
干预措施: Ketorolac Tromethamine with 4% Lidocaine hydrochloride (HCl) (Drug)
Ketorolac Tromethamine
干预措施: Ketorolac Tromethamine (Drug)
Ketorolac Tromethamine with 5% Lidocaine HCl
干预措施: Ketorolac Tromethamine with 5% Lidocaine HCl (Drug)
Ketorolac Tromethamine with 6% Lidocaine HCl
干预措施: 30 mg Ketorolac Tromethamine with 6% Lidocaine HCl (Drug)
结局指标
主要结局
Maximum Observed Plasma Concentration (Cmax)
时间窗: 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)
时间窗: 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-∞)
时间窗: 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
次要结局
- 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)