Pharmacokinetics and Relative Bioavailability of Intranasal vs Intramuscular Olanzapine in Healthy Adult Participants
A Phase 1, Open-Label, Two-Sequence, Five-Period, Single Ascending Dose Study to Assess the Pharmacokinetics, Safety, and Tolerability of Intranasal Olanzapine and Relative Bioavailability Compared to Olanzapine Intramuscular Injection in Healthy Adult Participants
This is a Phase 1, open-label, 5-period, 2-sequence, single ascending dose study designed to assess the pharmacokinetics, dose proportionality, safety, and tolerability of NRL-1004 (olanzapine nasal spray), and to assess the relative bioavailability of NRL-1004, compared to olanzapine intramuscular injection (ZYPREXA IM), in healthy adult participants. The study will be conducted in a single clinical research unit (CRU).
Aperçu de l'étude
Statut
Statut
Les conditions
Les conditions
Intervention / Traitement
Intervention / Traitement
Type d'étude
Type d'étude
Inscription (Estimé)
Inscription
Phase
Phase
- La phase 1
Contacts et emplacements
Coordonnées de l'étude
Coordonnées de l'étude
- Nom: Stella Ngo, PhD
- Numéro de téléphone: (908) 499-2326
- E-mail: sngo@neurelis.com
Critères de participation
Critère d'éligibilité
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
-
A participant will be eligible for study participation if the participant meets all of the following criteria:
-
Male and female participants aged between 18 to 65 years, inclusive.
-
Body weight ≥50 kg and body mass index (BMI) within the range of 18.0 to 30.0 kg/m2 (inclusive).
-
Participants must be healthy and without clinically significant abnormalities as assessed at screening and at first CRU admission visit.
-
No clinically significant abnormality on 12-lead ECG.
-
Normal blood pressures and pulse rate at screening and at first CRU admission visit.
-
If male, meets one of the following criteria:
- Is able to procreate and agrees to use one of the accepted contraceptive regimens and not to donate sperm from the first study drug administration to at least 90 days after the last drug administration.
- Is unable to procreate; defined as surgically sterile
-
If female, meets one of the following criteria:
- Is of childbearing potential and agrees to use an acceptable contraceptive method.
- Is of non-childbearing potential, defined as surgically sterile or is in a postmenopausal state.
-
Exclusion Criteria:
-
A participant will be excluded from the study if the participant meets any of the following criteria:
- Female who is pregnant or plans to become pregnant, or who is lactating or plans to be lactating during the study.
- Clinically significant cardiac, cardio- or cerebrovascular, respiratory, gastrointestinal, endocrine, hematologic, psychiatric, renal, hepatic, pulmonary, immunologic, dermatologic or nervous system disorders.
- History of or current postural orthostatic tachycardia syndrome, or orthostatic hypotension at screening and at first CRU admission.
- Current or history of psychiatric or psychotic diagnosis.
- Evidence or history of suicidal ideation as per the C-SSRS administered at screening and at first CRU admission, violence, or homicidality.
- Major surgery or open biopsy within 90 days prior to screening or expected/scheduled to have such procedure(s) performed during the study.
- Any other conditions or unstable diseases/disorders which may affect the ability of the participant to comply with the protocol requirements, jeopardize the safety of the participant, or impact the interpretation of the study results.
- Any clinical or laboratory measurements assessed by the Investigator as clinically relevant.
- Positive blood screen for human immunodeficiency virus (HIV-1/2), hepatitis B surface antigen (HBsAg), or hepatitis C virus antibody (HCV Ab) at screening.
- History of drug abuse or alcohol abuse within 12 months prior to Screening, and/or unwilling to refrain from such use throughout the study.
- History of smoking or use of tobacco or other nicotine-containing products within 3 months prior to screening and unwilling to refrain throughout the study.
- Use of medical or recreational cannabinoid use and unwilling to refrain throughout the study.
- Positive drug screen for alcohol, cotinine, or illicit drug/substance of abuse.
- Presence of acute conditions that could interfere with IN administration and drug absorption.
- National Institute of Health (NIH) Toolbox Odor Identification test score of 0 at screening.
- Current use of any drugs that may affect the absorption, metabolism, or elimination of study drugs, and that such treatment cannot be discontinued at least 4 weeks prior to screening and throughout the study.
- Unwilling to refrain from intake of food or consumption of caffeine-containing drinks that affect CYP1A2 activity throughout the course of the study.
- Use of any prescription medication within 14 days or 5 half-lives prior to the first dose of study drug or during the study unless approved by the Investigator. (Hormonal contraceptives or hormone replacement therapy are allowed.)
- Use of any over-the-counter medications within 14 days or 5 half lives prior to Screening and throughout the study unless approved by the Investigator.
- History of hypersensitivity or anaphylactic reactions to the active ingredient or any excipients of study drugs.
- Received an investigational drug within 30 days or within 5 half-lives or twice the duration of the biological effect of the investigational drug in previous study prior to screening.
- Inadequate or difficult venous access.
- Donation of plasma in the 7 days prior to the first study drug administration, or donation of 500 mL or more of blood in the 56 days prior to the first study drug administration.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation séquentielle
- Masquage: Aucun (étiquette ouverte)
Nombre de bras
Armes et Interventions
Groupe de participants / BrasGroupe de participants / Bras |
Intervention / TraitementIntervention / Traitement |
|---|---|
|
Expérimental: NRL 1004 25 mg/mL solution
NRL-1004 (olanzapine nasal spray), 25 mg/mL solution |
Olanzapine nasal spray |
|
Expérimental: NRL-1004 50 mg/mL solution
NRL-1004 (olanzapine nasal spray), 50 mg/mL solution |
Olanzapine nasal spray |
|
Expérimental: NRL-1004 75 mg/mL solution
NRL-1004 (olanzapine nasal spray), 75 mg/mL solution |
Olanzapine nasal spray |
|
Expérimental: NRL-1004 100 mg/mL solution
NRL-1004 (olanzapine nasal spray), 100 mg/mL solution |
Olanzapine nasal spray |
|
Comparateur actif: ZYPREXA IM 10mg/vial
ZYPREXA IntraMuscular (olanzapine) Injection, Powder, for Solution for Intramuscular use, 10 mg/vial |
Olanzapine IM injection |
Que mesure l'étude ?
Principaux critères de jugement
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Pharmacokinetic parameters of olanzapine in plasma
Délai: Time zero to 14 days postdose
|
Maximum observed plasma concentration (Cmax) |
Time zero to 14 days postdose
|
|
Pharmacokinetic parameters of olanzapine in plasma
Délai: Time zero to 14 days postdose
|
Time to maximum plasma concentration (Tmax) |
Time zero to 14 days postdose
|
|
Pharmacokinetic parameters of olanzapine in plasma
Délai: Time zero to 14 days postdose
|
Area under the plasma concentration time curve (AUC) from time zero to the last quantifiable concentration (AUC0-t) |
Time zero to 14 days postdose
|
|
Pharmacokinetic parameters of olanzapine in plasma
Délai: Time zero to 14 days postdose
|
AUC from time zero extrapolated to infinity (AUC0-inf) |
Time zero to 14 days postdose
|
|
Pharmacokinetic parameters of olanzapine in plasma
Délai: Time zero to 14 days postdose
|
Partial AUC from time zero to 2 hours postdose (AUC0-2 h) |
Time zero to 14 days postdose
|
|
Pharmacokinetic parameters of olanzapine in plasma
Délai: Time zero to 14 days postdose
|
Partial AUC from time zero to 24 hours postdose (AUC0-24 h) |
Time zero to 14 days postdose
|
|
Pharmacokinetic parameters of olanzapine in plasma
Délai: Time zero to 14 days postdose
|
Terminal phase half-life (t½) |
Time zero to 14 days postdose
|
|
Pharmacokinetic parameters of olanzapine in plasma
Délai: Time zero to 14 days postdose
|
Terminal phase rate constant (λz) |
Time zero to 14 days postdose
|
|
Pharmacokinetic parameters of olanzapine in plasma
Délai: Time zero to 14 days postdose
|
Apparent clearance (CL/F) |
Time zero to 14 days postdose
|
|
Pharmacokinetic parameters of olanzapine in plasma
Délai: Time zero to 14 days postdose
|
Apparent volume of distribution (Vz/F) |
Time zero to 14 days postdose
|
|
Pharmacokinetic parameters of olanzapine in plasma
Délai: Time zero to 14 days postdose
|
Relative bioavailability (Frel) |
Time zero to 14 days postdose
|
Collaborateurs et enquêteurs
Parrainer
Parrainer
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Estimé)
Début de l'étude
Achèvement primaire (Estimé)
Achèvement primaire
Achèvement de l'étude (Estimé)
Achèvement de l'étude
Dates d'inscription aux études
Première soumission
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Première publication
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour publiée
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Troubles bipolaires et apparentés
- Comportement moteur aberrant dans la démence
- Manifestations neurologiques
- Maladies du système nerveux
- Spectre de la schizophrénie et autres troubles psychotiques
- Les troubles mentaux
- Symptômes comportementaux
- Manifestations neurocomportementales
- Troubles de l'humeur
- Dyskinésies
- Troubles psychomoteurs
- Conditions pathologiques, signes et symptômes
- Comportement
- Signes et symptômes
- La schizophrénie
- Troubles psychotiques
- Trouble bipolaire
- Agitation psychomotrice
Autres numéros d'identification d'étude
Autres numéros d'identification d'étude
- OLAN.001.02
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Étudie un produit d'appareil réglementé par la FDA américaine
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