Trial Outcomes & Findings for A Bioavailability Crossover Study of Two Formulations of Lamotrigine Extended Release Tablets in Healthy Subjects (NCT NCT02821338)

Last Updated: 2020-05-01

Results Overview

Pre-dose, and post-dose 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 27, 30, 33, 36, 48, 72, 96, 120, 144 hours Lamotrigine and Lamictal have the same active ingredient "Lamotrigine."

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

30 participants

Primary outcome timeframe

144 hours

Results posted on

2020-05-01

Participant Flow

Participant milestones

Participant milestones
Measure	Sequence 1 (Test-Ref-Test-Ref) Sequence 1 - ABAB. The study was a single center, randomized, open-label, single dose, 2-treatment, 4-period, 2-sequence, fully replicated, crossover design in healthy male and female subjects. All completed subjects received two rounds of Lamictal and Lamotrigine. The following investigational products were administered in the fed state: Treatment A: A single 1-tablet dose of Lamotrigine 200 mg extended-release tablet (Test) Treatment B: A single 1-tablet dose of Lamictal XR 200 mg extended-release tablet (Reference)	Sequence 2 (Ref-Test-Ref-Test) Sequence 2 - BABA. The study was a single center, randomized, open-label, single dose, 2-treatment, 4-period, 2-sequence, fully replicated, crossover design in healthy male and female subjects. All completed subjects received two rounds of Lamictal and Lamotrigine. The following investigational products were administered in the fed state: Treatment A: A single 1-tablet dose of Lamotrigine 200 mg extended-release tablet (Test) Treatment B: A single 1-tablet dose of Lamictal XR 200 mg extended-release tablet (Reference)
Overall Study STARTED	15	15
Overall Study COMPLETED	12	13
Overall Study NOT COMPLETED	3	2

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Bioavailability Crossover Study of Two Formulations of Lamotrigine Extended Release Tablets in Healthy Subjects

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=30 Participants 30 participants Completed subjects received two rounds of Lamictal and Lamotrigine.
Age, Continuous	32 years n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	15 Participants n=5 Participants
Race (NIH/OMB) White	14 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	30 participants n=5 Participants
BMI	26.05 kg/m^2 STANDARD_DEVIATION 2.54 • n=5 Participants

PRIMARY outcome

Timeframe: 144 hours

Population: Fully replicated crossover study (all completed subjects received two rounds of Lamictal and Lamotrigine). Completed participants contributed two data points for each treatment, however, some subjects provided one or partial data point.

Pre-dose, and post-dose 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 27, 30, 33, 36, 48, 72, 96, 120, 144 hours Lamotrigine and Lamictal have the same active ingredient "Lamotrigine."

Outcome measures

Outcome measures
Measure	Generic Lamotrigine Extended Release Tablet n=44 data points Lamotrigine Extended Release (generic)	Brand Lamictal XR Tablet n=45 data points Lamictal XR (brand)
Area Under the Lamotrigine Concentration vs. Time Curve From Sample Time Point 0 Hour to Sample Time Point 144 Hour.	119966.6 h*ng/mL Standard Deviation 32391.0	121969.5 h*ng/mL Standard Deviation 33663.6

PRIMARY outcome

Timeframe: 144 hours

Population: Fully replicated crossover design (all completed subjects received two rounds of Lamictal and Lamotrigine). Completed participants contributed two data points for each treatment, however, some subjects provided one or partial data point.

Area Under the Lamotrigine Concentrations vs. time curve from sample time point 0 hour to sample time point 144hours plus extrapolation to infinity of the terminal concentration slope. This describes the total exposure to Lamotrigine. Sampling times include: Pre-dose, and post-dose 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 27, 30, 33, 36, 48, 72, 96, 120, 144 hours. Lamotrigine and Lamictal have the same active ingredient.

Outcome measures

Outcome measures
Measure	Generic Lamotrigine Extended Release Tablet n=43 data points Lamotrigine Extended Release (generic)	Brand Lamictal XR Tablet n=44 data points Lamictal XR (brand)
AUC 0-Inf	128824.9 h*ng/mL Standard Deviation 39291.6	134410.3 h*ng/mL Standard Deviation 47446.8

PRIMARY outcome

Timeframe: 2 to 144 hours

The maximum concentration of the Lamotrigine achieved in specified time frame for each treatment. Sampling times include: post-dose 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 27, 30, 33, 36, 48, 72, 96, 120, 144 hours. Lamotrigine and Lamictal have the same active ingredient.

Outcome measures

Outcome measures
Measure	Generic Lamotrigine Extended Release Tablet n=45 Data points Lamotrigine Extended Release (generic)	Brand Lamictal XR Tablet n=46 Data points Lamictal XR (brand)
Cmax	2338.9 ng/mL Standard Deviation 353.2	2244.6 ng/mL Standard Deviation 341.2

OTHER_PRE_SPECIFIED outcome

Timeframe: 2 to 144 hours

Population: Fully replicate crossover design (all completed subjects received two rounds of Lamictal and Lamotrigine). Completed participants contributed two data points for each treatment, however, some subjects provided one or partial data point.

Time from 0 concentration sample point to the Cmax sample point. Sampling times include: post-dose 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 27, 30, 33, 36, 48, 72, 96, 120, 144 hours.

Outcome measures

Outcome measures
Measure	Generic Lamotrigine Extended Release Tablet n=45 data points Lamotrigine Extended Release (generic)	Brand Lamictal XR Tablet n=46 data points Lamictal XR (brand)
Tmax	10 hours Interval 4.0 to 27.0	22 hours Interval 10.0 to 48.0

OTHER_PRE_SPECIFIED outcome

Timeframe: 2 to 144 hours

Apparent elimination rate constant, estimated by linear regression of the terminal linear portion of the log concentration versus time curve. Sampling times include: post-dose 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 27, 30, 33, 36, 48, 72, 96, 120, 144 hours.

Outcome measures

Outcome measures
Measure	Generic Lamotrigine Extended Release Tablet n=43 data points Lamotrigine Extended Release (generic)	Brand Lamictal XR Tablet n=44 data points Lamictal XR (brand)
λZ	0.0218 per hour Standard Deviation 0.0067	0.0221 per hour Standard Deviation 0.0067

OTHER_PRE_SPECIFIED outcome

Timeframe: 2 to 144 hours

It is the terminal elimination half-life, calculated as ln(2)/λZ. Sampling times include: post-dose 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 27, 30, 33, 36, 48, 72, 96, 120, 144 hours.

Outcome measures

Outcome measures
Measure	Generic Lamotrigine Extended Release Tablet n=43 data points Lamotrigine Extended Release (generic)	Brand Lamictal XR Tablet n=44 data points Lamictal XR (brand)
Thalf	34.77 hours Standard Deviation 10.57	34.56 hours Standard Deviation 11.34

Adverse Events

Generic Lamotrigine Extended Release Tablet

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Brand Lamictal XR Tablet

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Generic Lamotrigine Extended Release Tablet n=30 participants at risk Lamotrigine Extended Release (generic)	Brand Lamictal XR Tablet n=30 participants at risk Lamictal XR (brand)
Investigations Blood Pressure Systolic Increased	6.7% 2/30 • Number of events 2	3.3% 1/30 • Number of events 1
Investigations Drug Screen Positive	6.7% 2/30 • Number of events 2	3.3% 1/30 • Number of events 1
Investigations Heart Rate Increased	3.3% 1/30 • Number of events 1	3.3% 1/30 • Number of events 1
Investigations Liver Function Test Increased	0.00% 0/30	3.3% 1/30 • Number of events 1
Nervous system disorders Headache	6.7% 2/30 • Number of events 3	0.00% 0/30
Nervous system disorders Paraesthesia	3.3% 1/30 • Number of events 1	3.3% 1/30 • Number of events 1
Cardiac disorders Tachycardia	6.7% 2/30 • Number of events 2	3.3% 1/30 • Number of events 1
Cardiac disorders Bradycardia	0.00% 0/30	3.3% 1/30 • Number of events 1
Gastrointestinal disorders Diarrhoea	3.3% 1/30 • Number of events 1	6.7% 2/30 • Number of events 2
Gastrointestinal disorders Nausea	3.3% 1/30 • Number of events 1	0.00% 0/30
Skin and subcutaneous tissue disorders Acne	3.3% 1/30 • Number of events 1	0.00% 0/30
Skin and subcutaneous tissue disorders Ecchymosis	0.00% 0/30	3.3% 1/30 • Number of events 1
Skin and subcutaneous tissue disorders Rash	0.00% 0/30	3.3% 1/30 • Number of events 1
Infections and infestations Gastroenteritis	0.00% 0/30	3.3% 1/30 • Number of events 1
Infections and infestations Upper Respiratory Tract Infection	0.00% 0/30	3.3% 1/30 • Number of events 1
Injury, poisoning and procedural complications Laceration	0.00% 0/30	3.3% 1/30 • Number of events 1
Injury, poisoning and procedural complications Skin Abrasion	3.3% 1/30 • Number of events 1	0.00% 0/30
Musculoskeletal and connective tissue disorders Musculoskeletal Pain	3.3% 1/30 • Number of events 1	3.3% 1/30 • Number of events 1
Respiratory, thoracic and mediastinal disorders Nasal Congestion	3.3% 1/30 • Number of events 1	3.3% 1/30 • Number of events 1
General disorders Vessel Puncture Site Pain	0.00% 0/30	3.3% 1/30 • Number of events 1

Additional Information

Office of Generic Drugs, Center for Drug Evaluation and Research

US Food and Drug Administration

Phone: 240-402-7920

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60