Comparison of Pharmacokinetic Profiles of Two Nicotine Gu... | NCT01847443

Comparison of Pharmacokinetic Profiles of Two Nicotine Gu... | NCT01847443 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Test nicotine gum (2 mg)	Experimental	A single dose of Nicotine Mint Gum (2 mg) to be chewed.	Drug: Nicotine (2 mg)
Test nicotine gum (4 mg)	Experimental	A single dose of Nicotine Mint Gum (4 mg) to be chewed.	Drug: Nicotine (4 mg)
Reference nicotine gum (2 mg)	Active Comparator	A single dose of reference nicotine gum (2 mg) to be chewed.	Drug: Nicotine (2 mg)
Reference nicotine gum (4 mg)	Active Comparator	A single dose of reference nicotine gum (4 mg) to be chewed.	Drug: Nicotine (4 mg)

Name	Type	Description	Arm Group Labels	Other Names
Nicotine (2 mg)	Drug	2 mg nicotine gum in two formulations	Reference nicotine gum (2 mg) Test nicotine gum (2 mg)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Area Under the Curve From Time 0 to Time 't' [AUC(0-t)] of Nicotine 2 mg Test and Reference Product	AUC(0-t) for 2 mg test was compared with 2 mg reference gum	Blood samples to be collected from baseline to 12 hours post dose
AUC(0-t) of Nicotine 4 mg Test and Reference Product	AUC(0-t) of Nicotine 4 mg test was compared with 4 mg reference gum	Blood samples to be collected from baseline to 12 hours post dose
Maximum Observed Concentration (Cmax) of Nicotine 2 mg Test and Reference Product	Cmax for 2 mg test was compared with 2 mg reference gum	Blood samples to be collected from baseline to 12 hours post dose
Cmax of Nicotine 4 mg Test and Reference Product	Cmax for 4 mg test was compared with 4 mg reference gum	Blood samples to be collected from baseline to 12 hours post-dose

Secondary Outcomes

Measure	Description	Time Frame
Time to Maximum Observed Concentration (Tmax) of Nicotine 2 mg Test and Reference Products, and Nicotine 4 mg Test and Reference Products	Tmax for 2 mg test was compared with 2 mg reference gum, and 4 mg test was compared with 4 mg reference gum	Blood samples to be collected from baseline to 12 hours post dose

Contacts/Locations Module

Name	Affiliation	Role
GSK Clinical Trials	GlaxoSmithKline	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Celerion - BELFAST		Belfast	Northern Ireland	BT9 6AD	United Kingdom

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
30027479	Derived	Du D. A Single-Dose, Crossover-Design Bioequivalence Study Comparing Two Nicotine Gum Formulations in Healthy Subjects. Adv Ther. 2018 Aug;35(8):1169-1180. doi: 10.1007/s12325-018-0752-7. Epub 2018 Jul 19.

Arm/Group Information

ID	Title	Description
FG000	2mg Mint Gum/4mg Ref Gum/4mg Mint Gum/2mg Ref Gum	Participants randomly received 2mg nicotine mint gum or 4mg reference (ref) nicotine gum or 4mg nicotine mint gum or 2mg ref nicotine gum once daily on Day 1 of treatment period 1. After a 2-7 day washout period, participants were returned to the next treatment period until all four treatment periods were completed.
FG001	4mg Ref Gum/2mg Ref Gum/2mg Mint Gum/4mg Mint Gum	Participants randomly received 4mg ref nicotine gum or 2mg ref nicotine gum or 2mg nicotine mint gum or 4mg nicotine mint gum once daily on Day 1 of treatment period 1. After a 2-7 day washout period, participants were returned to the next treatment period until all four treatment periods were completed.
FG002	2mg Ref Gum/4mg Mint Gum/4mg Ref Gum/2mg Mint Gum	Participants randomly received 2mg ref nicotine gum or 4mg nicotine mint gum or 4mg ref nicotine gum or 2mg nicotine mint gum once daily on Day 1 of treatment period 1. After a 2-7 day washout period, participants were returned to the next treatment period until all four treatment periods were completed.
FG003	4mg Mint Gum/2mg Mint Gum/2mg Ref Gum/4mg Ref Gum	Participants randomly received 4mg nicotine mint gum or 2mg nicotine mint gum or 2mg ref nicotine gum or 4mg ref nicotine gum once daily on Day 1 of treatment period 1. After a 2-7 day washout period, participants were returned to the next treatment period until all four treatment periods were completed.

Periods

Title

Milestones

Reasons Not Completed

Study Period 1

Type	Comment	Milestone Data
STARTED		FG00021 subjects FG00121 subjects FG00221 subjects FG00321 subjects
COMPLETED		FG00021 subjects FG00120 subjects FG00221 subjects FG00321 subjects
NOT COMPLETED		FG0000 subjects FG0011 subjects FG0020 subjects FG0030 subjects

Type	Comment	Reasons
Withdrawal by Subject		FG0000 subjects FG0011 subjects FG0020 subjects FG003

Washout Period Before Study Period 2

Type	Comment	Milestone Data
STARTED		FG00021 subjects FG00120 subjects FG00221 subjects FG003

Study Period 2

Type	Comment	Milestone Data
STARTED		FG00019 subjects FG00119 subjects FG00221 subjects FG003

Washout Period Before Study Period 3

Type	Comment	Milestone Data
STARTED		FG00019 subjects FG00119 subjects FG00221 subjects FG003

Study Period 3

Type	Comment	Milestone Data
STARTED		FG00018 subjects FG00119 subjects FG00221 subjects FG003

Washout Period Before Study Period 4

Type	Comment	Milestone Data
STARTED		FG00018 subjects FG00119 subjects FG00221 subjects FG003

Study Period 4

Type	Comment	Milestone Data
STARTED		FG00016 subjects FG00119 subjects FG00221 subjects FG003

Baseline Characteristics Module

ID	Title	Description
BG000	Total Participants

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

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

Area Under the Curve From Time 0 to Time 't' [AUC(0-t)] of Nicotine 2 mg Test and Reference Product

AUC(0-t) for 2 mg test was compared with 2 mg reference gum

Bioequivalence evaluable subjects' population: participants randomized to 1 of 4 treatment sequences; took atleast one dose of study medication (both test and reference) in 2 mg dose and/or in 4 mg doses; did not have any adverse event assimilated to vomiting in first 4 h post-treatment; and did not have baseline nicotine concentration >5% of Cmax.

Posted

Mean

Standard Deviation

hr*ng/mL

Blood samples to be collected from baseline to 12 hours post dose

ID	Title	Description
OG000	Test Nicotine Gum (2 mg)	A single dose of Nicotine Mint Gum (2 mg) to be chewed.
OG001	Reference Nicotine Gum (2 mg)

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Test Nicotine Gum (2 mg)	A single dose of Nicotine Mint Gum (2 mg) to be chewed.

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
GSK Response Center	GlaxoSmithKline	866-435-7343

ID	Term
D016540	Smoking Cessation

ID	Term
D015438	Health Behavior
D001519	Behavior

Intervention Browse Module

ID	Term
D009538	Nicotine

ID	Term
D012991	Solanaceous Alkaloids
D000470	Alkaloids
D006571	Heterocyclic Compounds
D011725	Pyridines

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Null hypothesis stated that there was no difference between the test and reference gums in AUC(0-t)	ANOVA				Ratio of Geometric means	1.107			2-Sided	90	1.070	1.147				Yes	Non-Inferiority or Equivalence	Bioequivalence was to be established between the test and reference treatment if the 90% CI of ratio of geometric means (Test/Reference) was included within the bioequivalence limits of (0.80, 1.25)

Secondary

Time to Maximum Observed Concentration (Tmax) of Nicotine 2 mg Test and Reference Products, and Nicotine 4 mg Test and Reference Products

Tmax for 2 mg test was compared with 2 mg reference gum, and 4 mg test was compared with 4 mg reference gum

Posted

Median

Full Range

Blood samples to be collected from baseline to 12 hours post dose

ID	Title	Description
OG000	Test Nicotine Gum (2 mg)	A single dose of Nicotine Mint Gum (2 mg) to be chewed.
OG001	Reference Nicotine Gum (2 mg)	A single dose of Reference Nicotine Gum (2 mg) to be chewed.
OG002	Test Nicotine Gum (4 mg)	A single dose of Nicotine Mint Gum (4 mg) to be chewed.
OG003	Reference Nicotine Gum (4 mg)	A single dose of Reference Nicotine Gum (4 mg) to be chewed.

Units	Counts
Participants	OG00062 OG00162 OG00273 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000.75(0.5 to 1.0) OG0010.75(0.5 to 1.5) OG0020.75(0.5 to 1.5) OG003

Secondary

Apparent Terminal Elimination Half-life (T1/2) of Nicotine 2 mg Test and Reference Products, and Nicotine 4 mg Test and Reference Products

T1/2 of 2 mg test was compared with 2 mg reference gum, and 4 mg test was compared with 4 mg reference gum

Posted

Median

Full Range

Blood samples to be collected from baseline to 12 hours post dose

ID	Title	Description
OG000	Test Nicotine Gum (2 mg)	A single dose of Nicotine Mint Gum (2 mg) to be chewed.
OG001	Reference Nicotine Gum (2 mg)	A single dose of Reference Nicotine Gum (2 mg) to be chewed.
OG002	Test Nicotine Gum (4 mg)	A single dose of Nicotine Mint Gum (4 mg) to be chewed.
OG003	Reference Nicotine Gum (4 mg)	A single dose of Reference Nicotine Gum (4 mg) to be chewed.

Units	Counts
Participants	OG00062 OG00162 OG00273 OG003

Title

Denominators

Categories

Title	Measurements
	OG0002.12(1.4 to 3.4) OG0012.03(1.2 to 4.2) OG0022.01(1.3 to 4.1) OG003

Secondary

Apparent Terminal Elimination Rate Constant (Kel) of Nicotine 2 mg Test and Reference Products, and Nicotine 4 mg Test and Reference Products

Kel for 2 mg test was compared with 2 mg reference gum, and 4 mg test was compared with 4 mg reference gum

Posted

Median

Full Range

1/hr

Blood samples to be collected from baseline to 12 hours post dose

ID	Title	Description
OG000	Test Nicotine Gum (2 mg)	A single dose of Nicotine Mint Gum (2 mg) to be chewed.
OG001	Reference Nicotine Gum (2 mg)	A single dose of Reference Nicotine Gum (2 mg) to be chewed.
OG002	Test Nicotine Gum (4 mg)	A single dose of Nicotine Mint Gum (4 mg) to be chewed.
OG003	Reference Nicotine Gum (4 mg)	A single dose of Reference Nicotine Gum (4 mg) to be chewed.

Units	Counts
Participants	OG00062 OG00162 OG00273 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000.33(0.2 to 0.5) OG0010.34(0.2 to 0.6) OG0020.34(0.2 to 0.5) OG003

Secondary

Area Under Concentration-time Curve From Time 0 Extrapolated to ∞ [AUC(0-∞)] of Nicotine 2 mg Test and Reference Products, and Nicotine 4 mg Test and Reference Products

AUC(0-∞) for 2mg test was compared with 2 mg reference gum, and 4 mg test was compared with 4 mg reference gum

Posted

Mean

Standard Deviation

hr*ng/mL

Blood samples to be collected from baseline to 12 hours post dose

ID	Title	Description
OG000	Test Nicotine Gum (2 mg)	A single dose of Nicotine Mint Gum (2 mg) to be chewed.
OG001	Reference Nicotine Gum (2 mg)	A single dose of Reference Nicotine Gum (2 mg) to be chewed.
OG002	Test Nicotine Gum (4 mg)	A single dose of Nicotine Mint Gum (4 mg) to be chewed.
OG003	Reference Nicotine Gum (4 mg)	A single dose of Reference Nicotine Gum (4 mg) to be chewed.

Units	Counts
Participants	OG00062 OG00162 OG00273 OG003

Title

Denominators

Categories

Title	Measurements
	OG00012.56± 4.409 OG00111.20± 3.955 OG00224.60± 7.845 OG003

Primary

AUC(0-t) of Nicotine 4 mg Test and Reference Product

AUC(0-t) of Nicotine 4 mg test was compared with 4 mg reference gum

Bioequivalence evaluable subjects' population: participants randomized to 1of 4 treatment sequences; took atleast one dose of study medication (both test and ref) in 2 mg dose and/or in 4 mg doses; did not have any AE assimilated to vomiting in first 4h post-treatment; and did not have baseline nicotine concentration >5% of Cmax.

Posted

Mean

Standard Deviation

hr*ng/mL

Blood samples to be collected from baseline to 12 hours post dose

ID	Title	Description
OG000	Test Nicotine Gum (4 mg)	A single dose of Nicotine Mint Gum (4 mg) to be chewed.
OG001	Reference Nicotine Gum (4 mg)	A single dose of Reference Nicotine Gum (4 mg) to be chewed.

Units	Counts
Participants	OG00073 OG00173

Title

Denominators

Categories

Title	Measurements
	OG00023.44± 7.593 OG00121.50± 6.874

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Null hypothesis stated that there was no difference between the test and reference gums in AUC(0-t)	ANOVA				Ratio of Geometric means	1.098			2-Sided	90	1.061	1.137				Yes	Non-Inferiority or Equivalence	Bioequivalence was to be established between the test and reference treatment if the 90% CI of ratio of geometric means (Test/Reference) was included within the bioequivalence limits of (0.80, 1.25)

Primary

Maximum Observed Concentration (Cmax) of Nicotine 2 mg Test and Reference Product

Cmax for 2 mg test was compared with 2 mg reference gum

Posted

Mean

Standard Deviation

ng/mL

Blood samples to be collected from baseline to 12 hours post dose

ID	Title	Description
OG000	Test Nicotine Gum (2 mg)	A single dose of Nicotine Mint Gum (2 mg) to be chewed.
OG001	Reference Nicotine Gum (2 mg)	A single dose of Reference Nicotine Gum (2 mg) to be chewed.

Units	Counts
Participants	OG00062 OG00162

Title

Denominators

Categories

Title	Measurements
	OG0003.93± 1.232 OG0013.72± 1.289

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Null hypothesis stated that there was no difference between the test and reference gums in Cmax	ANOVA				Ratio of Geometric means	1.044			2-Sided	90	1.002	1.089				Yes	Non-Inferiority or Equivalence	Bioequivalence was to be established between the test and reference treatment if the 90% CI of ratio of geometric means (Test/Reference) was included within the bioequivalence limits of (0.80, 1.25)

Primary

Cmax of Nicotine 4 mg Test and Reference Product

Cmax for 4 mg test was compared with 4 mg reference gum

Posted

Mean

Standard Deviation

ng/mL

Blood samples to be collected from baseline to 12 hours post-dose

ID	Title	Description
OG000	Test Nicotine Gum (4 mg)	A single dose of Nicotine Mint Gum (4 mg) to be chewed.
OG001	Reference Nicotine Gum (4 mg)	A single dose of Reference Nicotine Gum (4 mg) to be chewed.

Units	Counts
Participants	OG00073 OG00173

Title

Denominators

Categories

Title	Measurements
	OG0007.49± 1.720 OG0016.98± 1.777

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Null hypothesis stated that there was no difference between the test and reference gums in Cmax	ANOVA				Ratio of Geometric means	1.071			2-Sided	90	1.028	1.116				Yes	Non-Inferiority or Equivalence	Bioequivalence was to be established between the test and reference treatment if the 90% CI of ratio of geometric means (Test/Reference) was included within the bioequivalence limits of (0.80, 1.25)