Single Dose, Crossover, Pharmacokinetic Evaluation of a New Naloxone Nasal Swab, Naloxone Nasal Spray, and Intramuscular Naloxone Injection in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 76
- 试验地点
- 1
- 主要终点
- Pharmacokinetics of Various Naloxone Administrations (Maximum plasma concentration (Cmax))-Phase 1
研究概览
简要总结
The study consists of two Phases with the first phase (Pilot Phase) divided into two sub phases.
In each study phase, subjects will be admitted to the clinical unit from 10 hours prior to the first drug administration on Day -1 until approximately 12 hours following the last study drug administration. Screening of alcohol and drugs of abuse will be performed before the first study drug administration. For female subjects, a pregnancy test will be performed before the first drug administration. Clinical nasal irritation rating and the Brief Smell Identification Test will be performed at screening.
详细描述
The study consists of two Phases with the first phase (Pilot Phase) divided into two sub phases.
In each study phase, subjects will be admitted to the clinical unit from 10 hours prior to the first drug administration on Day -1 until approximately 12 hours following the last study drug administration. Screening of alcohol and drugs of abuse will be performed before the first study drug administration. For female subjects, a pregnancy test will be performed before the first drug administration. Clinical nasal irritation rating and the Brief Smell Identification Test will be performed at screening.
Phases 1A and , 1B, and 1C (Pilot Phase) The first sub-phase, Phase 1A, will be an inpatient, 5-period, 5-treatment, crossover study involving 10 healthy subjects.
In Phase 1A of the study, qualified subjects will receive one of the following treatment in the morning, after a 10 hour overnight fast:
- Treatment-1: Single 0.4 mg IM naloxone injection will be administered (1 mL of 0.4 mg/mL injection, into the gluteus maximus muscle using a 23-gauge needle).
- Treatment-2: Single 4 mg intranasal naloxone spray will be administered in one nostril (0.1 mL of 4 mg/0.1 mL spray, based on the prescribing information and approved Instructions for Use).
- Treatment-3: Single 8 mg naloxone nasal swab administered as one swab in one nostril, swirled 3 times around the inside of the nasal mucosa.
- Treatment-4: Single 4 mg naloxone nasal swab administered as one swab in one nostril, swirled 3 times around the inside of the nasal mucosa.
- Treatment-5: Single 12 mg naloxone nasal swab administered as one swab in one nostril, swirled 3 times around the inside of the nasal mucosa.
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Provision of signed and dated informed consent form (ICF)
- •Stated willingness to comply with all study procedures and availability for the duration of the study
- •Healthy adult male or female
- •If female, meets 1 of the following criteria:
- •Is of childbearing potential and agrees to use an acceptable contraceptive method. Acceptable contraceptive methods include:
- •Abstinence from heterosexual intercourse from the first study drug administration through to at least 30 days after the last dose of the study drug
- •1 of the following highly-effective contraceptive methods, used from at least 28 days prior to the first study drug administration through to at least 30 days after the last dose of the study drug: Systemic contraceptives (combined birth control pills, injectable/implant/insertable hormonal birth control products, transdermal patch) Intrauterine device (with or without hormones) Male partner vasectomized at least 6 months prior to the first study drug administration
- •The following effective contraceptive method, used from the first study drug administration through to at least 30 days after the last dose of the study drug:
- •Male condom with diaphragm/cervical cap plus spermicide Or
- •Male partner has had a vasectomy less than 6 months prior to dosing, and the female subject agrees to use an additional acceptable contraceptive method from the first study drug administration through to at least 30 days after the last dose of the study drug Or
- •Is of non-childbearing potential, defined as surgically sterile (i.e. has undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation) or is in a postmenopausal state (i.e. at least 1 year without menses without an alternative medical condition prior to the first study drug administration)
- •Aged at least 18 years but not older than 55 years
- •Body mass index (BMI) within 18.5 kg/m2 to 30.0 kg/m2, inclusively
- •Non- or ex-smoker (An ex smoker is defined as someone who completely stopped using nicotine products for at least 180 days prior to the first study drug administration)
- •Have no clinically significant diseases captured in the medical history or evidence of clinically significant findings on the physical examination (including vital signs), ECG, and/or nasal cavity examination, as determined by an investigator
排除标准
- •Female who is lactating at screening
- •Female who is pregnant according to the pregnancy test at screening or prior to the first study drug administration
- •Seated blood pressure higher than 140/90 mmHg at screening or prior to the first study drug administration
- •History of significant hypersensitivity to naloxone or any related products (including excipients of the formulations) as well as severe hypersensitivity reactions (like angioedema) to any drugs
- •Presence or history of significant gastrointestinal, liver or kidney disease, or any other condition that is known to interfere with drug absorption, distribution, metabolism or excretion, or known to potentiate or predispose to undesired effects
- •History of significant cardiovascular, pulmonary, hematologic, neurological, psychiatric, endocrine, immunologic or dermatologic disease
- •Presence of clinically significant ECG abnormalities at the screening visit, as defined by medical judgment
- •Any intranasal conditions including nostril piercing, abnormal nasal anatomy, nasal symptoms (i.e., blocked and/or runny nose, nasal polyps, etc.), or having a product sprayed into the nasal cavity prior to drug administration
- •Current or recent upper respiratory tract infection (within 28 days before the first study drug administration)
- •Maintenance therapy with any drug or significant history of drug dependency or alcohol abuse (> 3 units of alcohol per day, intake of excessive alcohol, acute or chronic)
- •Any clinically significant illness in the 28 days prior to the first study drug administration
- •Use of any prescription drugs (with the exception of hormonal contraceptives or hormone replacement therapy) in the 28 days prior to the first study drug administration, that in the opinion of an investigator would put into question the status of the participant as healthy
- •Any history of tuberculosis
- •Positive test result for alcohol and/or drugs of abuse at screening or prior to the first drug administration
- •Positive screening results to HIV Ag/Ab combo, hepatitis B surface antigen or hepatitis C virus antibody tests
- •Any other clinically significant abnormalities at screening that would, in the opinion of an investigator, increase the subject's risk of participation, jeopardize complete participation in the study, or compromise interpretation of study data
- •Inclusion in a previous group for this clinical study (for Phase 2 only)
- •Intake of naloxone in the 28 days prior to the first study drug administration
- •Intake of an Investigational Product (IP) in the 28 days prior to the first study drug administration
- •Donation of 50 mL or more of blood in the 28 days prior to the first study drug administration
- •Donation of 500 mL or more of blood (Canadian Blood Services, Hema-Quebec, clinical studies, etc.) in the 56 days prior to the first study drug administration
研究组 & 干预措施
Naloxone IM Injection
Single 0.4 mg IM naloxone injection will be administered (1 mL of 0.4 mg/mL injection, into the gluteus maximus muscle using a 23-gauge needle).
干预措施: IM Naloxone Injection (Drug)
Intranasal Naloxone Spray
Single 4 mg intranasal naloxone spray will be administered in one nostril (0.1 mL of 4 mg/0.1 mL spray, based on the prescribing information and approved Instructions for Use).
干预措施: Naloxone Nasal Spray (Drug)
Single 8 mg naloxone nasal swab-Swirl method
Single 8 mg naloxone nasal swab administered as one swab in one nostril, swirled 3 times around the inside of the nasal mucosa.
干预措施: Naloxone Nasal Swab (Drug)
Single 4 mg naloxone nasal swab-Swirl method
Single 4 mg naloxone nasal swab administered as one swab in one nostril, swirled 3 times around the inside of the nasal mucosa.
干预措施: Naloxone Nasal Swab (Drug)
Single 12 mg naloxone nasal swab-Swirl method
Single 12 mg naloxone nasal swab administered as one swab in one nostril, swirled 3 times around the inside of the nasal mucosa.
干预措施: Naloxone Nasal Swab (Drug)
Single 12 mg naloxone nasal swab-Squeeze method
Single 12 mg naloxone nasal swab administered into the nasal cavity - administered in one nostril and using two fingers to squeeze outside of both nostrils.
干预措施: Naloxone Nasal Swab (Drug)
Single 12 mg naloxone nasal swab in each nostril-Squeeze method
Two 12 mg naloxone nasal swabs in both nostrils- administered one per nostril and using two fingers to squeeze outside of both nostrils (two doses given sequentially)
干预措施: Naloxone Nasal Swab (Drug)
Single 8 mg naloxone nasal swab in each nostril-Squeeze method
Two 8 mg naloxone nasal swab in both nostrils - administered one per nostril and using two fingers to squeeze outside of both nostrils (two doses given sequentially)
干预措施: Naloxone Nasal Swab (Drug)
Single 12.5 mg naloxone nasal swab-Squeeze method
Single target naloxone nasal swab dose identified in Phase 1(12.5 mg) administered as one swab in one nostril, using the insert into nostril and squeeze method of administration
干预措施: Naloxone Nasal Swab (Drug)
Single 12.5 mg naloxone nasal swab in each nostril-Squeeze method
Single target naloxone nasal swab dose identified in Phase 1 (12.5 mg) using the insert into each nostril and squeeze method of administration (two doses given in total).
干预措施: Naloxone Nasal Swab (Drug)
结局指标
主要结局
Pharmacokinetics of Various Naloxone Administrations (Maximum plasma concentration (Cmax))-Phase 1
时间窗: 17 days
To determine the pharmacokinetics (PK) of various naloxone intranasal swab doses (4, 8, and 12 mg) compared to intramuscular (IM) naloxone injection (0.4 mg dose) and naloxone nasal spray (4 mg dose) in healthy subjects. Maximum plasma concentration (Cmax) will be measured.
Pharmacokinetics of Various Naloxone Administrations (Area Under the Curve (AUC))-Phase 1
时间窗: 17 days
To determine the pharmacokinetics (PK) of various naloxone intranasal swab doses (4, 8, and 12 mg) compared to intramuscular (IM) naloxone injection (0.4 mg dose) and naloxone nasal spray (4 mg dose) in healthy subjects. Area Under the Curve (AUC)will be measured.
Bioavailability (Area Under the Curve (AUC))-Phase 2
时间窗: 13 days
To evaluate and compare the bioavailability of the identified nasal naloxone swab target dose from the Phase 1 (12.5 mg) and IM naloxone injection (0.4 mg). Area Under the Curve (AUC) will be measured.
Pharmacokinetics of Various Naloxone Administrations (Partial Area Under the Curve (AUC))-Phase 1
时间窗: 17 days
To determine the pharmacokinetics (PK) of various naloxone intranasal swab doses (4, 8, and 12 mg) compared to intramuscular (IM) naloxone injection (0.4 mg dose) and naloxone nasal spray (4 mg dose) in healthy subjects. Partial Area Under the Curve (AUC) will be measured.
Dose Selection (Maximum plasma concentration (Cmax))-Phase 1
时间窗: 17 days
To identify an appropriate target intranasal swab dose using comparative PK parameters with IM naloxone injection (0.4 mg) and naloxone nasal spray (4 mg dose) in healthy subjects. Maximum plasma concentration (Cmax) will be measured.
Bioavailability (Maximum plasma concentration (Cmax))-Phase 2
时间窗: 13 days
To evaluate and compare the bioavailability of the identified nasal naloxone swab target dose from the Phase 1 (12.5 mg) and IM naloxone injection (0.4 mg). Maximum plasma concentration (Cmax) will be measured.
Bioavailability (Partial Area Under the Curve (AUC))-Phase 2
时间窗: 13 days
To evaluate and compare the bioavailability of the identified nasal naloxone swab target dose from the Phase 1 (12.5 mg) and IM naloxone injection (0.4 mg). Partial Area Under the Curve (AUC) will be measured.
Dose Selection (Area Under the Curve (AUC))-Phase 1
时间窗: 17 days
To identify an appropriate target intranasal swab dose using comparative PK parameters with IM naloxone injection (0.4 mg) and naloxone nasal spray (4 mg dose) in healthy subjects. Area Under the Curve (AUC) will be measured.
Dose Selection (Partial Area Under the Curve (AUC))-Phase 1
时间窗: 17 days
To identify an appropriate target intranasal swab dose using comparative PK parameters with IM naloxone injection (0.4 mg) and naloxone nasal spray (4 mg dose) in healthy subjects. Partial Area Under the Curve (AUC) will be measured.
次要结局
- Safety of Naloxone Swab- (Treatment emergent adverse events (TEAEs))-Phase 1 and 2(17 days)
- Absorption Levels-Phase 2(13 days)
- Absorption Levels-Phase 1 and 2(17 days)
- Dose Proportionality-Phase 2(13 days)