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Bioavailability Study of Naloxone 5 Milligrams (mg) Intramuscular (IM) Autoinjector

2 mars 2022 mis à jour par: Pfizer

A PHASE 1 RANDOMIZED, OPEN-LABEL, SINGLE-DOSE, 3-TREATMENT CROSS-OVER STUDY TO EVALUATE RELATIVE BIOAVAILABILITY OF INTRAMUSCULAR INJECTION OF NALOXONE HCL 5 Milligrams (mg) [5mg/0.5 Milliliters (mL] USING A QUICKSHOT™ AUTOINJECTOR COMPARED TO 2 mg NALOXONE INTRAMUSCULAR INJECTION AND 2 mg NALOXONE INTRAVENOUS INJECTION IN HEALTHY ADULT PARTICIPANTS

To compare the plasma concentration (bioavailability) and safety of a single naloxone 5 mg autoinjector intramuscular (IM) injection to a single 2 mg IM injection (an approved safe dose) and to a single 2 mg bolus intravenous (IV) injection (an approved safe dose)

Aperçu de l'étude

Description détaillée

A randomized, open-label, 3-treatment, 6-sequences, 3-period Williams Square crossover single-dose, relative bioavailability study in healthy adult participants. The study includes Screening period, a Treatment period and a Follow-up contact (SoA). At least twelve (12) participants will be enrolled. If the number of evaluable participants falls below 12, participants may be replaced.

Type d'étude

Interventionnel

Inscription (Réel)

13

Phase

  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

    • Connecticut
      • New Haven, Connecticut, États-Unis, 06511
        • New Haven Clinical Research Unit

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 55 ans (Adulte)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

Participants are eligible to be included in the study only if all of the following criteria apply:

Age and Sex:

  1. Healthy male and/or female participants of non-childbearing potential, who, at the time of screening, are between the ages of 18 and 55 years, inclusive.

    Refer to protocol for reproductive criteria for male and female participants.

    Type of Participant and Disease Characteristics:

  2. Male and female participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, vital signs, 12-lead ECG, and/or clinical laboratory tests.
  3. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.

    Weight:

  4. BMI of 17.5 to 30.5 kg/m2; and a total body weight > 50 kg (110 lb).

Informed Consent:

5. Capable of giving signed informed consent as described in Appendix 1, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.

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Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

Medical Conditions:

  1. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
  2. Current or past diagnosis of any type of drug dependence within the past year will not be eligible to participate. History of alcohol abuse, dependence or binge drinking and/or any other illicit drug use within 6 months of screening. Binge drinking is hours. As a general rule, alcohol intake should not exceed 14 units per week (1 unit = 8 ounces (240 mL) beer, 1 ounce (30 mL) of 40% spirit or 3 ounces (90 mL) of wine).
  3. If fever is present within 7 days of admission or screening.
  4. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
  5. History of HIV infection, hepatitis B, or hepatitis C, positive testing for HIV, HBsAg, or HCVAb. Hepatitis B vaccination is allowed.
  6. Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.

    Prior/Concomitant Therapy:

  7. Use of prescription or nonprescription drugs and dietary and herbal supplements within 14 days or 5 half-lives (whichever is longer) prior to the first dose of study intervention. Prior/Concurrent Clinical Study Experience:
  8. Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer).

    Diagnostic Assessments:

  9. A positive urine drug test.
  10. Has participated in, is currently participating in, or is seeking treatment for substance-and/or alcohol-related disorders (excluding nicotine and caffeine).
  11. Has a positive alcohol breathalyzer test at screening or upon admission to the study center of Treatment Period. Positive results may be repeated and/or participants re-scheduled at the investigator's discretions.
  12. Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of supine rest. If BP is ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant's eligibility. Repeated BP tests should be spaced at least 5 minutes apart.
  13. Screening supine 12-lead ECG demonstrating a QTc interval > 450 msec or a QRS interval > 120 msec. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTc or QRS values should be used to determine the participant's eligibility.
  14. Participants with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study-specific laboratory and confirmed by a single repeat test, if deemed necessary:

    Abnormal platelet count and/or PT/INR; AST or ALT level ≥1.5 × ULN; Total bilirubin level ≥1.5 × ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ ULN.

    Other Exclusions:

  15. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.
  16. History of sensitivity to heparin or heparin-induced thrombocytopenia.
  17. Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of this protocol.
  18. History of hypersensitivity to naloxone or any of the components in the formulation of the study products.
  19. Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.

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Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Science basique
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation croisée
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: naloxone 5 mg IM autoinjector
participants will receive in random order, a single naloxone 5 mg IM autoinjector injection into the lateral thigh
5 mg (5 mg/0.5 mL) IM autoinjector injection into lateral thigh
Comparateur actif: naloxone 2 mg IM
participants will receive in random order, a single naloxone 2 mg IM injection into the gluteus muscle
2 mg IM (2mg/2 mL) injection into gluteal muscle
2 mg bolus IV (2mg/2 mL)
Comparateur actif: naloxone 2mg bolus IV
participants will receive in random order, a single naloxone 2 mg bolus IV injection
2 mg IM (2mg/2 mL) injection into gluteal muscle
2 mg bolus IV (2mg/2 mL)

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Maximum observed plasma naloxone concentration (Cmax) of a single 5 mg IM autoinjector injection compared to a 2 mg IM injection
Délai: predose, 2.5, 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 360, 480, and 1440 minutes after dose
Comparison of bioavailability
predose, 2.5, 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 360, 480, and 1440 minutes after dose
Area under the naloxone concentration versus time curve (AUC) from time zero to the last collection time (AUClast) of a single 5 mg IM autoinjector injection compared to a 2 mg IM injection
Délai: predose, 2.5, 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 360, 480, and 1440 minutes after dose
Comparison of bioavailability
predose, 2.5, 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, 360, 480, and 1440 minutes after dose

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
AUC from time zero to 2.5 minutes (AUC0-2.5)
Délai: predose and 2.5 minutes after dose
Pharmacokinetics all treatment arms
predose and 2.5 minutes after dose
AUC from time zero to 5 minutes (AUC0-5)
Délai: predose, 2.5 and 5 minutes after dose
Pharmacokinetics all treatment arms
predose, 2.5 and 5 minutes after dose
AUC from time zero to 15 minutes (AUC0-15)
Délai: predose, 2.5, 5, 10 and 15 minutes after dose
Pharmacokinetics all treatment arms
predose, 2.5, 5, 10 and 15 minutes after dose
AUC from time zero to 30 minutes (AUC0-30)
Délai: predose, 2.5, 5, 10, 15, and 30 minutes after dose
Pharmacokinetics all treatment arms
predose, 2.5, 5, 10, 15, and 30 minutes after dose
AUC from time zero extrapolated to infinity (AUCinf) [if data permit]
Délai: predose, 2.5, 5, 10, 15, 30, 60,90, 120, 180, 240, 360, 480, 1440 minutes after dose
Pharmacokinetics all treatment arms
predose, 2.5, 5, 10, 15, 30, 60,90, 120, 180, 240, 360, 480, 1440 minutes after dose
Time to maximum observed naloxone plasma concentration (Tmax) [if data permit],
Délai: predose, 2.5, 5, 10, 15, 30, 60,90, 120, 180, 240, 360, 480, 1440 minutes after dose
Pharmacokinetics all treatment arms
predose, 2.5, 5, 10, 15, 30, 60,90, 120, 180, 240, 360, 480, 1440 minutes after dose
Time for naloxone plasma concentration to decrease by one half (t1/2) [if data permit].
Délai: predose, 2.5, 5, 10, 15, 30, 60,90, 120, 180, 240, 360, 480, 1440 minutes after dose
Pharmacokinetics all treatment arms
predose, 2.5, 5, 10, 15, 30, 60,90, 120, 180, 240, 360, 480, 1440 minutes after dose
Number of participants with a clinically significant change from baseline physical examination
Délai: baseline to 28 days after last dose
Safety and tolerability all treatments
baseline to 28 days after last dose
Number of participants with a clinically significant change from baseline vital signs
Délai: baseline to 28 days after last dose
Safety and tolerability all treatments
baseline to 28 days after last dose
Number of participants with a clinically significant change from baseline clinical safety laboratory measurements
Délai: baseline to 28 days after last dose
Safety and tolerability all treatment arms
baseline to 28 days after last dose
Number of participants with clinically significant AEs from baseline
Délai: baseline to 28 days after last dose
Safety and tolerability all treatment arms
baseline to 28 days after last dose

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

6 octobre 2020

Achèvement primaire (Réel)

8 janvier 2021

Achèvement de l'étude (Réel)

8 janvier 2021

Dates d'inscription aux études

Première soumission

14 février 2022

Première soumission répondant aux critères de contrôle qualité

2 mars 2022

Première publication (Réel)

3 mars 2022

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

3 mars 2022

Dernière mise à jour soumise répondant aux critères de contrôle qualité

2 mars 2022

Dernière vérification

1 mars 2022

Plus d'information

Termes liés à cette étude

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

Non

Description du régime IPD

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Oui

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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