Lifestyle Modification and Lorcaserin for Weight Loss Maintenance

• Sponsor: University of Pennsylvania (Other)
• Overall Status: Completed
• CT.gov ID: NCT02388568
• Collaborator: Eisai Inc. (Industry)
• Enrollment: 137
• Location: 1
• Arms: 2
• Duration (Months): 29
• Patients Per Site Per Month: 4.7

Study Details

Study Description

Brief Summary

The proposed 12-month randomized controlled trial will assess the efficacy of lifestyle counseling, combined with lorcaserin (10 mg BID) or placebo, in maintaining weight loss achieved during a prior 14-week dietary run-in.

14-week run-in. To qualify for randomization, participants must lose ≥5% of initial weight in the 14-week dietary run-in. This loss will be achieved with the provision of weekly, group lifestyle counseling, which includes a 1000-1200 kcal/day portion-controlled diet that combines four daily servings of a liquid diet (HMR shakes) with an evening meal of a frozen-food entree (and a fruit and vegetable serving). More than 70% of participants are expected to achieve the 5% criterion loss during the 14-week run-in.

A total of 182 women and men with a BMI ≥33 and ≤55 kg/m2, without co-morbidities, or ≥30 and ≤55 kg/m2 (with a co-morbid cardiovascular disease (CVD) condition) will be enrolled in the 4-month run-in period. Prior to enrollment, all participants will have a history, physical exam, electrocardiogram (EKG), and appropriate blood tests. They will attend weekly group sessions for 14 weeks. Participants will have a brief medical visit at week 8 to check their health and blood tests will be repeated. The investigators anticipate that 136 (75%) participants will lose 5% or more of initial weight and qualify for randomization. Participants who do not lose 5% will be provided a list of weight loss resources (e.g., other programs) to facilitate their continued weight management.

12-month randomized trial with lorcaserin. A total of 136 participants who have lost 5% or more of initial weight in the run-in period will be randomly assigned, in double-blind fashion, to lorcaserin (10 mg BID) or matching placebo. To be eligible, participants must have a BMI (after prior weight loss) ≥30 kg/m2 (without co-morbidities) or greater than or equal to ≥27 (with a co-morbidity). Randomization will be performed by the Investigational Drug Service at the Hospital of the University of Pennsylvania. Prior to randomization, all participants will complete a second brief history and physical examination, as well as an EKG and blood tests. Medication will be dispensed at the randomization visit and at brief medical visits that follow. Over the 1 year, all participants will participate in 16 group lifestyle modification classes designed for weight loss maintenance, approximately half of which will be delivered by group conference call.

Primary outcome measure. The primary endpoint is change in body weight (in kg), as measured from randomization to month 12. The co-primary end-point is the percentage of participants in the two groups that, at month 12, maintained the ≥5% reduction in body weight achieved during the 14-week dietary run-in period. Secondary efficacy endpoints include changes in CVD risk factors, glycemic control, and quality of life, as measured from randomization to month 12. Exploratory endpoints include changes in these CVD and related outcomes, as measured at the start of the 14-week run-in period to month 12. The investigators also will examine the percentage of participants in the two groups who at month 12 achieved losses of ≥5%, ≥10%, and ≥15% of initial weight, as measured from the start of the run-in period.

Safety endpoints will include physical examination, electrocardiogram, adverse events (AEs), standard laboratory tests, and mental health assessed by the Columbia Suicidality Severity Rating Scale (C-SSRS) and Patient Health Questionnaire (PHQ-9).

Statistical Analysis. The planned sample size of 136 participants, with a 1:1 randomization ratio, assumes a 20% drop-out rate (at month 12) and was estimated to be adequate to evaluate the primary endpoint with power ≥90% (P=0.05, two-sided test). The investigators predict a difference in weight change between the two groups (from randomization to month 12) of 4 kg (SD=3.5). Pre-specified data analysis will be performed on the full analysis set, comprising all randomized individuals exposed to trial drug with at least one post-randomization weight assessment.

Condition or Disease	Intervention/Treatment	Phase
Obesity	Drug: Lorcaserin; Drug: Placebo	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 137 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized Controlled Trial of Lifestyle Modification and Lorcaserin for Weight Loss Maintenance
• Study Start Date: Jan 1, 2015
• Actual Primary Completion Date: Jun 1, 2017
• Actual Study Completion Date: Jun 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Lorcaserin plus Lifestyle Modification	Drug: Lorcaserin; Lorcaserin plus Lifestyle Modification
Placebo Comparator: Placebo plus Lifestyle Modification	Drug: Placebo; Placebo plus Lifestyle Modification

Outcome Measures

Primary Outcome Measures

1. Change in Weight (kg) [52 weeks post-randomization]

   This is the change in weight from randomization to week 52. This does not include the weight loss in the 14-week LCD.

2. Proportion Maintaining >= 5% Loss of Initial Weight [52 weeks post-randomization]

   This is the number of participants who maintained >=5% loss of initial weight in the randomization to week 52 trial period.

Secondary Outcome Measures

1. Body Weight (% Change) [52 weeks post-randomization]

   The % change in body weight from randomization to week 52.

2. Proportion Maintaining >= 10% Loss of Initial Weight [52 weeks post-randomization]

   This is the number of participants who maintained >=10% loss of initial weight in the randomization to week 52 trial period.

3. Body Weight [-14 week (start of LCD program) to week 52]

   This is the change in weight from baseline (screening visit) to the final week 52 medical assessment visit.

4. Body Weight (% Change) [-14 week (start of LCD program) to week 52]

   This is the change in weight from the baseline (screening visit) to the final week 52 medical assessment visit.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria (for the Randomized Controlled Trial)

1. Participants must have lost ≥ 5% of initial weight in the group lifestyle modification program (during the 14-week diet run-in period).

2. Participants must have a BMI ≥ 30 and ≤ 55 kg/m² or have a BMI ≥ 27 kg/m² with a obesity-related co-morbid condition

3. Age ≥ 21 years and ≤ 65

4. Eligible female patients will be:

• non-pregnant, evidenced by a negative urine dipstick pregnancy test

• non-lactating

• surgically sterile or postmenopausal, or they will agree to continue to use an accepted method of birth control during the study

1. Participants must have a primary care provider (PCP) who is responsible for providing routine care and have a reliable telephone service with which to participate in conference calls

Exclusion Criteria:

1. Pregnant or nursing (or plans to become pregnant in the next 18 months)

2. Current major depressive episode, active suicidal ideation, or history of suicide attempts

3. Use in the past 14 days of monoamine oxidase inhibitors, selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors (SNRI), tricyclics, lithium, triptans, antipsychotics, cabergoline, linezolid, tramadol, dextromethorphan, tryptophan, bupropion, St. John's Wort, or medicines to treat erectile dysfunction

4. Uncontrolled hypertension (systolic blood pressure ≥ 160 mm Hg, or diastolic blood pressure ≥ 100 mm Hg)

5. Type 1 diabetes or type 2 diabetes

6. A fasting glucose ≥ 126 mg/dl or HbA1c ≥ 6.5

7. Recent history of cardiovascular disease (e.g., myocardial infarction or stroke within the past 6 months), congestive heart failure, or heart block greater than first degree

8. Clinically significant hepatic or renal disease

9. Thyroid disease not controlled

10. History of malignancy (except for non-melanoma skin cancer)

11. Use of medications known to induce significant weight loss/gain, including chronic use of oral steroids

12. Psychiatric hospitalization within the past 6 months

13. Self-reported alcohol or substance abuse within the past 12 months, including at-risk drinking (current consumption of ≥ 14 alcoholic drinks per week)

14. Loss of ≥ 10 lb of body weight within the past 3 months

15. History of (or plans for) bariatric surgery

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Pennsylvania Center for Weight and Eating Disorders	Philadelphia	Pennsylvania	United States	19104

Sponsors and Collaborators

• University of Pennsylvania
• Eisai Inc.

Investigators

• Principal Investigator: Thomas A Wadden, Ph.D., University of Pennsylvania
• Principal Investigator: Robert I Berkowitz, M.D., University of Pennsylvania

Study Documents (Full-Text)

• Study Protocol - Jan 25, 2016
• Statistical Analysis Plan - Feb 19, 2014

More Information

Publications

None provided.

• Responsible Party: University of Pennsylvania
• ClinicalTrials.gov Identifier: NCT02388568
• Other Study ID Numbers: Eisai-819111
• First Posted: Mar 17, 2015
• Last Update Posted: Jun 11, 2018
• Last Verified: May 1, 2018

• Additional relevant MeSH terms: Weight Loss

Study Results

Participant Flow

Arm/Group Title	Lorcaserin Plus Lifestyle Modification	Placebo Plus Lifestyle Modification
Arm/Group Description	Lorcaserin: Lorcaserin plus Lifestyle Modification	Placebo: Placebo plus Lifestyle Modification
Period Title: Overall Study
STARTED	69	68
COMPLETED	59	53
NOT COMPLETED	10	15

Baseline Characteristics

Arm/Group Title	Lorcaserin Plus Lifestyle Modification	Placebo Plus Lifestyle Modification	Total
Arm/Group Description	Lorcaserin: Lorcaserin plus Lifestyle Modification	Placebo: Placebo plus Lifestyle Modification	Total of all reporting groups
Overall Participants	69	68	137
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45.4 (10.5)	47.7 (9.8)	46.1 (10.1)
Sex: Female, Male (Count of Participants)
Female	59 85.5%	59 86.8%	118 86.1%
Male	10 14.5%	9 13.2%	19 13.9%
Race/Ethnicity, Customized (Count of Participants)
Black or African American	49 71%	45 66.2%	94 68.6%
White	15 21.7%	18 26.5%	33 24.1%
Asian	2 2.9%	2 2.9%	4 2.9%
Multiracial or other	3 4.3%	3 4.4%	6 4.4%
Race/Ethnicity, Customized (Count of Participants)
Hispanic	4 5.8%	3 4.4%	7 5.1%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	168.8 (8.6)	165.7 (9.4)	167.2 (9.1)

Outcome Measures

1. Primary Outcome

Title	Change in Weight (kg)
Description	This is the change in weight from randomization to week 52. This does not include the weight loss in the 14-week LCD.
Time Frame	52 weeks post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lorcaserin Plus Lifestyle Modification	Placebo Plus Lifestyle Modification
Arm/Group Description	Lorcaserin: Lorcaserin plus Lifestyle Modification	Placebo: Placebo plus Lifestyle Modification
Measure Participants	69	68
Mean (Standard Error) [kg]	2.0 (0.8)	2.5 (0.8)

2. Primary Outcome

Title	Proportion Maintaining >= 5% Loss of Initial Weight
Description	This is the number of participants who maintained >=5% loss of initial weight in the randomization to week 52 trial period.
Time Frame	52 weeks post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lorcaserin Plus Lifestyle Modification	Placebo Plus Lifestyle Modification
Arm/Group Description	Lorcaserin: Lorcaserin plus Lifestyle Modification	Placebo: Placebo plus Lifestyle Modification
Measure Participants	69	68
Count of Participants [Participants]	38 55.1%	29 42.6%

3. Secondary Outcome

Title	Body Weight (% Change)
Description	The % change in body weight from randomization to week 52.
Time Frame	52 weeks post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lorcaserin Plus Lifestyle Modification	Placebo Plus Lifestyle Modification
Arm/Group Description	Lorcaserin: Lorcaserin plus Lifestyle Modification	Placebo: Placebo plus Lifestyle Modification
Measure Participants	69	68
Mean (Standard Error) [% change]	1.8 (0.8)	2.2 (0.8)

4. Secondary Outcome

Title	Proportion Maintaining >= 10% Loss of Initial Weight
Description	This is the number of participants who maintained >=10% loss of initial weight in the randomization to week 52 trial period.
Time Frame	52 weeks post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lorcaserin Plus Lifestyle Modification	Placebo Plus Lifestyle Modification
Arm/Group Description	Lorcaserin: Lorcaserin plus Lifestyle Modification	Placebo: Placebo plus Lifestyle Modification
Measure Participants	69	68
Count of Participants [Participants]	20 29%	20 29.4%

5. Secondary Outcome

Title	Body Weight
Description	This is the change in weight from baseline (screening visit) to the final week 52 medical assessment visit.
Time Frame	-14 week (start of LCD program) to week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lorcaserin Plus Lifestyle Modification	Placebo Plus Lifestyle Modification
Arm/Group Description	Lorcaserin: Lorcaserin plus Lifestyle Modification	Placebo: Placebo plus Lifestyle Modification
Measure Participants	69	68
Mean (Standard Error) [kg]	-9.4 (0.9)	-7.5 (1.0)

6. Secondary Outcome

Title	Body Weight (% Change)
Description	This is the change in weight from the baseline (screening visit) to the final week 52 medical assessment visit.
Time Frame	-14 week (start of LCD program) to week 52

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Lorcaserin Plus Lifestyle Modification	Placebo Plus Lifestyle Modification
Arm/Group Description	Lorcaserin: Lorcaserin plus Lifestyle Modification	Placebo: Placebo plus Lifestyle Modification
Measure Participants	69	68
Mean (Standard Error) [% change]	-7.8 (0.8)	-6.6 (0.9)

Adverse Events

Time Frame	Adverse events for phase 2 of the trial were reported from the time of randomization to 13 months after randomization. Safety assessments included recording adverse events at all clinic visits; a physical examination, fasting blood test, and urine pregnancy test (as appropriate) at randomization, and weeks 24 and 52 of phase 2; and nine brief medical visits to measure vital signs, review health, and administer the Columbia-Suicide Severity Rating Scale.
Arm/Group Title	Lorcaserin Plus Lifestyle Modification		Placebo Plus Lifestyle Modification
Arm/Group Description	Lorcaserin: Lorcaserin plus Lifestyle Modification		Placebo: Placebo plus Lifestyle Modification
All Cause Mortality
	Lorcaserin Plus Lifestyle Modification		Placebo Plus Lifestyle Modification
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/69 (0%)		0/68 (0%)
Serious Adverse Events
	Lorcaserin Plus Lifestyle Modification		Placebo Plus Lifestyle Modification
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/69 (2.9%)		8/68 (11.8%)
Cardiac disorders
Hypertension	0/69 (0%)		1/68 (1.5%)
Endocrine disorders
Sialolithiasis/sialadenitis	1/69 (1.4%)		0/68 (0%)
Gastrointestinal disorders
Cholelithiasis	0/69 (0%)		1/68 (1.5%)
Nervous system disorders
Vertigo	0/69 (0%)		1/68 (1.5%)
Reproductive system and breast disorders
Pregnancy	0/69 (0%)		1/68 (1.5%)
Respiratory, thoracic and mediastinal disorders
Pneumonia	0/69 (0%)		2/68 (2.9%)
Asthma Exacerbation	0/69 (0%)		1/68 (1.5%)
Lung nodules	0/69 (0%)		1/68 (1.5%)
Skin and subcutaneous tissue disorders
Staph cellulitis	1/69 (1.4%)		0/68 (0%)
Other (Not Including Serious) Adverse Events
	Lorcaserin Plus Lifestyle Modification		Placebo Plus Lifestyle Modification
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	56/69 (81.2%)		49/68 (72.1%)
Gastrointestinal disorders
Constipation	10/69 (14.5%)		3/68 (4.4%)
General disorders
Fatigue	11/69 (15.9%)		12/68 (17.6%)
Dry mouth	7/69 (10.1%)		3/68 (4.4%)
Dizziness	4/69 (5.8%)		2/68 (2.9%)
Musculoskeletal and connective tissue disorders
Musculoskeletal injury	3/69 (4.3%)		6/68 (8.8%)
Pain in extremity	2/69 (2.9%)		5/68 (7.4%)
Nervous system disorders
Headache	12/69 (17.4%)		7/68 (10.3%)
Respiratory, thoracic and mediastinal disorders
Upper respiratory infection	5/69 (7.2%)		7/68 (10.3%)
Asthma exacerbation	2/69 (2.9%)		4/68 (5.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.