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| ID | Type | Description | Link |
|---|---|---|---|
| ZRHR-PK-01-EU | Other Identifier | Philip Morris Products S.A. | |
| 2013-003097-27 | EudraCT Number |
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The primary objective of this clinical study is to evaluate the pharmacokinetic (PK) profile (rate and amount of nicotine absorbed) following a single use of the THS 2.2 compared to the PK profiles from a single use of a conventional cigarette (CC) and from a single use of nicotine nasal spray (NNS).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| THS 2.2 then CC | Active Comparator | Each subject will follow the below study design:
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| CC then THS 2.2 | Active Comparator | Each subject will follow the below study design:
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| THS 2.2 then NNS | Active Comparator | Each subject will follow the below study design:
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| NNS then THS 2.2 | Active Comparator | Each subject will follow the below study design:
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| THS 2.2 | Other | Single use of the Tobacco Heating System 2.2 (THS 2.2) |
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| Measure | Description | Time Frame |
|---|---|---|
| Maximum Concentration (Cmax) of Nicotine Following Single Use of THS 2.2, CC and NNS | Derived from multiple blood sampling on Day 1 and Day 3 (1 blood sampling pre-product use and multiple blood sampling over 24 hours post-product use). Geometric Least Squares means are provided. | 3 days |
| Area Under the Plasma Concentration-Time Curve From Time Zero (Pre-product Use) to Last Time Point [AUC(0-last)] Following Single Use of THS 2.2, CC and NNS | Derived from multiple blood sampling on Day 1 and Day 3 (1 blood sampling pre-product use and multiple blood sampling over 24 hours post-product use). Geometric Least Squares means are provided. | 3 days |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Christelle Haziza, PhD | Philip Morris Products S.A. | Study Chair |
| Adrian Johnston Stewart, MD | Celerion GB Ltd. | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Celerion GB Ltd, 22-24 Lisburn Road | Belfast | BT9 6AD | United Kingdom |
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Enrolled population = 62 subjects = 62 randomized as described below:
Study initiated (first subject screened): 01 November 2013
At admission (Day -1), all the subjects performed a product trial (THS 2.2 and subsequently NNS).
From enrollment, they were asked to remain abstinent from smoking for at least 24 hours (Day 0) before being randomized on Day 1 into 1 of the 4 sequences.
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| ID | Title | Description |
|---|---|---|
| FG000 | THS 2.2 Then CC | Each subject will follow the below study design:
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| FG001 | CC Then THS 2.2 | Each subject will follow the below study design:
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| FG002 | THS 2.2 Then NNS | Each subject will follow the below study design:
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| FG003 | NNS Then THS 2.2 | Each subject will follow the below study design:
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| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Washout Period of 1 Day (Day 0) |
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| First Intervention (Day 1) |
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| Washout Period of 1 Day (Day 2) |
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| Second Intervention (Day 3) |
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PK population: all randomized subjects who completed at least 1 of the single-use days, with at least 1 derived PK parameter. No subjects were excluded due to major protocol deviations impacting the evaluation of the results.
62 randomized: 44 in Group 1, 18 in Group 2
60 completers: 42 in Group 1 (2 discontinued), 18 in Group 2
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| ID | Title | Description |
|---|---|---|
| BG000 | Group 1 | This population comprises the following sequences:
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| BG001 | Group 2 | This population comprises the following sequences:
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| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Maximum Concentration (Cmax) of Nicotine Following Single Use of THS 2.2, CC and NNS | Derived from multiple blood sampling on Day 1 and Day 3 (1 blood sampling pre-product use and multiple blood sampling over 24 hours post-product use). Geometric Least Squares means are provided. | PK populations consisted of all the randomized subjects who completed at least 1 of the single use days (Days 1 or 3), and for whom at least 1 PK parameter could be derived. Subjects with major protocol deviations that impacted the evaluability of the results were excluded from the PK populations. | Posted | Least Squares Mean | 95% Confidence Interval | ng/mL | 3 days |
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From the informed consent form (ICF( signature until the end of the safety follow-up period (7 days after discharge of the subject)
The safety was assessed in the safety population, consisting of 62 subjects: 44 subjects in Group 1, 18 subjects in Group 2. This population includes all the subjects exposed to THS 2.2 and NNS from the product trials on Day -1.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Group 1 | This population comprises the following sequences:
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dizziness | Nervous system disorders | MedDRA (16.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Christelle HAZIZA, PhD | Philip Morris Products S.A. | +41 (58) 242 2625 | Christelle.Haziza@pmi.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 11, 2014 | Mar 2, 2020 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 8, 2014 | Mar 2, 2020 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D012907 | Smoking |
| ID | Term |
|---|---|
| D001519 | Behavior |
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| CC | Other | Single use of subject's own conventional cigarette (CC) |
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| NNS | Other | Single administration of 1 mg of nicotine |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| COMPLETED |
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| NOT COMPLETED |
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| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| International Organization for Standardization (ISO) nicotine level | Number | participants |
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| OG001 | CC - Group 1 | The geometric least squares mean presented below takes into consideration the data of the subjects who were randomized in the following sequences:
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| OG002 | THS 2.2 - Group 2 | The geometric least squares mean presented below takes into consideration the data of the subjects who were randomized in the following sequences:
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| OG003 | NNS - Group 2 | The geometric least squares mean presented below takes into consideration the data of the subjects who were randomized in the following sequences:
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| Primary | Area Under the Plasma Concentration-Time Curve From Time Zero (Pre-product Use) to Last Time Point [AUC(0-last)] Following Single Use of THS 2.2, CC and NNS | Derived from multiple blood sampling on Day 1 and Day 3 (1 blood sampling pre-product use and multiple blood sampling over 24 hours post-product use). Geometric Least Squares means are provided. | PK populations consisted of all the randomized subjects who completed at least 1 of the single use days (Days 1 or 3), and for whom at least 1 PK parameter could be derived. Subjects with major protocol deviations that impacted the evaluability of the results were excluded from the PK populations. | Posted | Least Squares Mean | 95% Confidence Interval | h*ng/mL | 3 days |
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| 0 |
| 44 |
| 15 |
| 44 |
| EG001 | Group 2 | This population comprises the following sequences:
| 0 | 18 | 6 | 18 |
| Headache | Nervous system disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Presyncope | Nervous system disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Pallor | Vascular disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Haematuria | Renal and urinary disorders | MedDRA (16.0) | Non-systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (16.0) | Non-systematic Assessment |
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We confirm we have the contractual provisions in place which specifies that in no event will the study site be allowed to disclose to any third party (or publicly release) any information obtained through the study without the CRO's prior written consent which in turn cannot provide such consent without Sponsor's approval unless such publication is made to satisfy regulatory requirements.
The Intellectual Property rights and research results from the present study belongs to the Sponsor.