Nicotine Pharmacokinetics and Pharmacodynamics, Safety and Tolerability of P3P
21 de enero de 2020 actualizado por: Philip Morris Products S.A.
A Single-center, Open-label, Randomized, Crossover Study to Investigate the Nicotine Pharmacokinetic Profile, Pharmacodynamics, Safety and Tolerability of Four P3P Variants in Smoking Healthy Adult Subjects
This is a single-center, open-label, randomized, crossover study to evaluate the pharmacokinetic (PK) profiles of four P3P variants (differing in nicotine aerosol particle size, nicotine concentration and in the absence or presence of a flavoring system), following a fixed puffing regimen and an ad libitum use period.
In addition, pharmacodynamic (PD) effects (subjective effects and related behavioral assessments), as well as human puffing topography, will be evaluated, to provide further insights on product safety, acceptance, and use.
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Descripción detallada
The goal of the proposed study is to evaluate the pharmacokinetic profiles of four P3P variants. Variants with two different nicotine contents (1 mg/product and 2 mg/product), two different nicotine aersol particle sizes and presence/absence of a flavoring system will be tested to identify which one would yield plasma nicotine concentrations as close as possible to those achieved after smoking a single cigarette. All of the subjects will initially use the lowest nicotine content product (P3P 3). Subject will continue the study using the three remaining products (P3P 1, P3P 2 and P3P 4) containing 2 mg nicotine/product in a randomly assigned sequence.
Two product use regimens: fixed puffing and ad libitum use will be applied to provide insight into nicotine absorption. The fixed puffing regimen with consistent use conditions across subjects will be applied in order to minimize variability. The 1 hour ad libitum use period will provide information on nicotine PK and product acceptance when subjects use the P3P according to their own puffing behavior which is closer to a real-world setting.
Safety and tolerability will also be assessed throughout the study.
Tipo de estudio
Intervencionista
Inscripción (Actual)
19
Fase
- No aplica
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
-
-
Ticino
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Arzo, Ticino, Suiza, 6864
- CROSS Research
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-
Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
21 años a 65 años (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
Sí
Géneros elegibles para el estudio
Todos
Descripción
Inclusion criteria:
- Subject has signed the Informed Consent Form (ICF) and is able to understand the information provided in the ICF.
- Subject is between 21 and 65 years old.
- Subject is Caucasian.
- Smoking, healthy subject as judged by the Investigator or designee based on available assessments from the screening period.
- Subject has been smoking at least 10 commercially available cigarettes per day at least for the last 4 weeks prior to Screening Visit. Smoking status will be verified based on a urinary cotinine test (cotinine ≥ 200 ng/mL).
- Subject has been smoking for at least the last 3 years prior to Screening Visit.
- Subject does not plan to quit smoking in the next 2 months after the Screening Visit.
Exclusion criteria:
- Female subject is pregnant or breastfeeding.
- Female subject uses estrogen-containing hormonal contraception or hormone replacement therapy.
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Otro
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación cruzada
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Comparador activo: Product Sequence 1
Subjects will be exposed to P3P 3 on day 1 of the study, then randomized to follow a sequence of product exposure comprised of: P3P 2 on Day 2; P3P 4 on Day 3; P3P 1 on Day 4 |
2 mg of nicotine; no flavor; nicotine powder particle size of 2.25 ± 0.2 μm
2 mg of nicotine; flavor; nicotine powder particle size of 2.25 ± 0.2 μm
1 mg of nicotine; flavor; nicotine powder particle size of 2.25 ± 0.2 μm
2 mg of nicotine; flavor; nicotine powder particle size of 1.8 ± 0.2 μm
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Comparador activo: Product Sequence 2
Subjects will be exposed to P3P 3 on day 1 of the study, then randomized to follow a sequence of product exposure comprised of: P3P 4 on Day 2; P3P 1 on Day 3; P3P 2 on Day 4 |
2 mg of nicotine; no flavor; nicotine powder particle size of 2.25 ± 0.2 μm
2 mg of nicotine; flavor; nicotine powder particle size of 2.25 ± 0.2 μm
1 mg of nicotine; flavor; nicotine powder particle size of 2.25 ± 0.2 μm
2 mg of nicotine; flavor; nicotine powder particle size of 1.8 ± 0.2 μm
|
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Comparador activo: Product Sequence 3
Subjects will be exposed to P3P 3 on day 1 of the study, then randomized to follow a sequence of product exposure comprised of: P3P 1 on Day 2; P3P 2 on Day 3; P3P 4 on Day 4 |
2 mg of nicotine; no flavor; nicotine powder particle size of 2.25 ± 0.2 μm
2 mg of nicotine; flavor; nicotine powder particle size of 2.25 ± 0.2 μm
1 mg of nicotine; flavor; nicotine powder particle size of 2.25 ± 0.2 μm
2 mg of nicotine; flavor; nicotine powder particle size of 1.8 ± 0.2 μm
|
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Comparador activo: Product Sequence 4
Subjects will be exposed to P3P 3 on day 1 of the study, then randomized to follow a sequence of product exposure comprised of: P3P 1 on Day 2; P3P 4 on Day 3; P3P 2 on Day 4 |
2 mg of nicotine; no flavor; nicotine powder particle size of 2.25 ± 0.2 μm
2 mg of nicotine; flavor; nicotine powder particle size of 2.25 ± 0.2 μm
1 mg of nicotine; flavor; nicotine powder particle size of 2.25 ± 0.2 μm
2 mg of nicotine; flavor; nicotine powder particle size of 1.8 ± 0.2 μm
|
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Comparador activo: Product Sequence 5
Subjects will be exposed to P3P 3 on day 1 of the study, then randomized to follow a sequence of product exposure comprised of: P3P 2 on Day 2; P3P 1 on Day 3; P3P 4 on Day 4 |
2 mg of nicotine; no flavor; nicotine powder particle size of 2.25 ± 0.2 μm
2 mg of nicotine; flavor; nicotine powder particle size of 2.25 ± 0.2 μm
1 mg of nicotine; flavor; nicotine powder particle size of 2.25 ± 0.2 μm
2 mg of nicotine; flavor; nicotine powder particle size of 1.8 ± 0.2 μm
|
|
Comparador activo: Product Sequence 6
Subjects will be exposed to P3P 3 on day 1 of the study, then randomized to follow a sequence of product exposure comprised of: P3P 4 on Day 2; P3P 2 on Day 3; P3P 1 on Day 4 |
2 mg of nicotine; no flavor; nicotine powder particle size of 2.25 ± 0.2 μm
2 mg of nicotine; flavor; nicotine powder particle size of 2.25 ± 0.2 μm
1 mg of nicotine; flavor; nicotine powder particle size of 2.25 ± 0.2 μm
2 mg of nicotine; flavor; nicotine powder particle size of 1.8 ± 0.2 μm
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Plasma Nicotine Concentration-time Profile
Periodo de tiempo: Derived from multiple blood sampling (measured at 2 mins, 4 mins, 7 mins, 10 mins, 15 mins, 30 mins, 1 hour, 2 hours, and 4 hours post-product use) on Days 1, 2, 3 and 4
|
To measure the plasma nicotine concentration-time profile of four P3P variants from the fixed puffing regimen, following correction of baseline nicotine levels.
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Derived from multiple blood sampling (measured at 2 mins, 4 mins, 7 mins, 10 mins, 15 mins, 30 mins, 1 hour, 2 hours, and 4 hours post-product use) on Days 1, 2, 3 and 4
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Maximum Plasma Concentration [Cmax]
Periodo de tiempo: Derived from multiple blood sampling (measured at 2 mins, 4 mins, 7 mins, 10 mins, 15 mins, 30 mins, 1 hour, 2 hours, and 4 hours post-product use) on Days 1, 2, 3 and 4
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To measure the maximum nicotine plasma concentration [Cmax] of four P3P variants from the fixed puffing regimen, following correction of baseline nicotine levels.
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Derived from multiple blood sampling (measured at 2 mins, 4 mins, 7 mins, 10 mins, 15 mins, 30 mins, 1 hour, 2 hours, and 4 hours post-product use) on Days 1, 2, 3 and 4
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Time to the Maximum Nicotine Concentration [Tmax]
Periodo de tiempo: Derived from multiple blood sampling (measured at 2 mins, 4 mins, 7 mins, 10 mins, 15 mins, 30 mins, 1 hour, 2 hours, and 4 hours post-product use) on Days 1, 2, 3 and 4
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To measure the time to maximum nicotine concentration [Tmax] of four P3P variants from the fixed puffing regimen, following correction of baseline nicotine levels.
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Derived from multiple blood sampling (measured at 2 mins, 4 mins, 7 mins, 10 mins, 15 mins, 30 mins, 1 hour, 2 hours, and 4 hours post-product use) on Days 1, 2, 3 and 4
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Area Under the Concentration-time Curve From Start of Product Use (T0 Fix) to 4 Hours [AUCfix (0-4h)]
Periodo de tiempo: Derived from multiple blood sampling (measured at 2 mins, 4 mins, 7 mins, 10 mins, 15 mins, 30 mins, 1 hour, 2 hours, and 4 hours post-product use) on Days 1, 2, 3 and 4
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To measure the area under the plasma concentration-time curve of four P3P variants from the fixed puffing regimen, following correction of baseline nicotine levels.
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Derived from multiple blood sampling (measured at 2 mins, 4 mins, 7 mins, 10 mins, 15 mins, 30 mins, 1 hour, 2 hours, and 4 hours post-product use) on Days 1, 2, 3 and 4
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Plasma Nicotine Concentration-time Profile
Periodo de tiempo: Derived from multiple blood sampling (measured at 10 mins, 20 mins, 30 mins, 40 mins, 1 hour, 2 hours, and 4 hours during and post-ad libitum use) on Days 1, 2, 3 and 4
|
To measure the plasma nicotine concentration-time profile of four P3P variants from the ad libitum use period, following correction of baseline nicotine levels.
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Derived from multiple blood sampling (measured at 10 mins, 20 mins, 30 mins, 40 mins, 1 hour, 2 hours, and 4 hours during and post-ad libitum use) on Days 1, 2, 3 and 4
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Peak Plasma Nicotine Concentration [Cpeak]
Periodo de tiempo: Derived from multiple blood sampling (measured at 10 mins, 20 mins, 30 mins, 40 mins, 1 hour, 2 hours, and 4 hours during and post-ad libitum use) on Days 1, 2, 3 and 4
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To measure the Peak plasma nicotine concentration [Cpeak] of four P3P variants from the ad libitum use period, following correction of baseline nicotine levels.
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Derived from multiple blood sampling (measured at 10 mins, 20 mins, 30 mins, 40 mins, 1 hour, 2 hours, and 4 hours during and post-ad libitum use) on Days 1, 2, 3 and 4
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Time to Peak Plasma Nicotine Concentration [Tpeak]
Periodo de tiempo: Derived from multiple blood sampling (measured at 10 mins, 20 mins, 30 mins, 40 mins, 1 hour, 2 hours, and 4 hours during and post-ad libitum use) on Days 1, 2, 3 and 4
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To measure the time to peak plasma nicotine concentration [Tpeak] of four P3P variants from the ad libitum use period, following correction of baseline nicotine levels.
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Derived from multiple blood sampling (measured at 10 mins, 20 mins, 30 mins, 40 mins, 1 hour, 2 hours, and 4 hours during and post-ad libitum use) on Days 1, 2, 3 and 4
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Trough Plasma Nicotine Concentration [Ctrough]
Periodo de tiempo: Derived from multiple blood sampling (measured at 10 mins, 20 mins, 30 mins, 40 mins, 1 hour, 2 hours, and 4 hours during and post-ad libitum use) on Days 1, 2, 3 and 4
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To measure the trough plasma nicotine concentration [Ctrough] of four P3P variants from the ad libitum use period, following correction of baseline nicotine levels.
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Derived from multiple blood sampling (measured at 10 mins, 20 mins, 30 mins, 40 mins, 1 hour, 2 hours, and 4 hours during and post-ad libitum use) on Days 1, 2, 3 and 4
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Average of Plasma Nicotine Concentration From T0 ad Lib to 1 Hour [Caverage]
Periodo de tiempo: Derived from multiple blood sampling (measured at 10 mins, 20 mins, 30 mins, 40 mins, 1 hour during ad libitum use) on Days 1, 2, 3 and 4
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To measure the average of plasma nicotine concentration [Caverage], of four P3P variants from the ad libitum use period, following correction of baseline nicotine levels
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Derived from multiple blood sampling (measured at 10 mins, 20 mins, 30 mins, 40 mins, 1 hour during ad libitum use) on Days 1, 2, 3 and 4
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Area Under the Concentration-time Curve From Start of Product Use (T0 ad Lib) to 4 Hours [AUCad Lib (0-4h)]
Periodo de tiempo: Derived from multiple blood sampling (measured at 10 mins, 20 mins, 30 mins, 40 mins, 1 hour, 2 hours, and 4 hours during and post-ad libitum use) on Days 1, 2, 3 and 4
|
To measure the area under the plasma concentration-time curve of four P3P variants from the ad libitum use period, following correction of baseline nicotine levels.
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Derived from multiple blood sampling (measured at 10 mins, 20 mins, 30 mins, 40 mins, 1 hour, 2 hours, and 4 hours during and post-ad libitum use) on Days 1, 2, 3 and 4
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AUC of Craving for a Cigarette During and After the Fixed Puffing Regimen
Periodo de tiempo: During and up to 4 hours post-product use on days 1, 2, 3 and 4
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Measured on a Visual Analogue Scale (VAS) of 0 (no craving) to 100 (strong craving).
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During and up to 4 hours post-product use on days 1, 2, 3 and 4
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AUC Craving for a Cigarette During and After the ad Libitum Use Period
Periodo de tiempo: During and up to 4 hours post-product use on days 1, 2, 3 and 4
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Measured on a Visual Analogue Scale (VAS) of 0 (no craving) to 100 (strong craving).
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During and up to 4 hours post-product use on days 1, 2, 3 and 4
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Product Evaluation
Periodo de tiempo: Within 60 minutes after the ad libitum use session on days 1, 2, 3 and 4
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Measured with an adapted version of the modified Cigarette Evaluation Questionnaire (adapted mCEQ) following the ad libitum use period.
Assessed on a 7-point scale, ranging from 1 (not at all) to 7 (extremely).
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Within 60 minutes after the ad libitum use session on days 1, 2, 3 and 4
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Sensory Parameters
Periodo de tiempo: Within 60 minutes after the ad libitum use session on days 1, 2, 3 and 4
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Measured with a Sensory Questionnaire (SQ) following the ad libitum use period.
Response to each question is assessed on a 7-point scale, ranging from 1 (not at all) to 7 (extremely).
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Within 60 minutes after the ad libitum use session on days 1, 2, 3 and 4
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Human Puffing Topography (HPT) Parameters (Puff Volume) of Four P3P Variants During the Fixed Puffing Regimen Period.
Periodo de tiempo: During fixed puffing product use on days 1, 2, 3 and 4
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Descriptive statistics of total puff volume and average puff volume, of four P3P variants, during the fixed puffing regimen period.
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During fixed puffing product use on days 1, 2, 3 and 4
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Human Puffing Topography (HPT) Parameters (Puff Volume) of Four P3P Variants During the ad Libitum Use Period.
Periodo de tiempo: During ad libitum product use on days 1, 2, 3 and 4
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Descriptive statistics of total puff volume and average puff volume, of four P3P variants, during the ad libitum use period.
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During ad libitum product use on days 1, 2, 3 and 4
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Amount of Powder Aerosolized From P3P From the Fixed Puffing Regimen.
Periodo de tiempo: Before and after fixed puffing product use on days 1, 2, 3 and 4
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Descriptive statistics of P3P weight before use, and after use, for the fixed puffing regimen.
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Before and after fixed puffing product use on days 1, 2, 3 and 4
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Amount of Powder Aerosolized From P3P From the ad Libitum Use Period (Per Product Used).
Periodo de tiempo: Before and after ad libitum product use on days 1, 2, 3 and 4
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P3P weight before use, and after use, to determine the amount of powder aerosolized from P3P during Ad Libitum use (per product used).
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Before and after ad libitum product use on days 1, 2, 3 and 4
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Investigadores
- Investigador principal: Milko Radicioni, MD, CROSS Research, Arzo, Ticino, Switzerland
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
7 de noviembre de 2017
Finalización primaria (Actual)
1 de febrero de 2018
Finalización del estudio (Actual)
2 de mayo de 2018
Fechas de registro del estudio
Enviado por primera vez
22 de noviembre de 2017
Primero enviado que cumplió con los criterios de control de calidad
5 de diciembre de 2017
Publicado por primera vez (Actual)
12 de diciembre de 2017
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
31 de enero de 2020
Última actualización enviada que cumplió con los criterios de control de calidad
21 de enero de 2020
Última verificación
1 de enero de 2020
Más información
Términos relacionados con este estudio
Palabras clave
Otros números de identificación del estudio
- P3P-PK-01-CH
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
NO
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
No
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
No
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .
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