Trial Outcomes & Findings for Zonisamide for Weight Reduction in Obese Adults (NCT NCT00275834)

NCT ID: NCT00275834

Last Updated: 2017-01-12

Results Overview

The primary endpoint was weight loss at 1-year, Month-12 weight minus baseline weight, in kilograms.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 225 participants
• Primary outcome timeframe: 1 year
• Results posted on: 2017-01-12

Participant Flow

The study was conducted at Duke University Medical Center between 2006 and 2011.

Participants are considered to have completed the study if they returned for final study visit. The number completed represents participants who stayed on study drug during the trial plus participants who discontinued study drug during the trial but continued to be followed by study team and completed the final visit assessments.

Participant milestones

Measure	Placebo Zonisamide 100 mg and placebo capsules were prepared in accordance with Good Manufacturing Practice (GMP) guidelines in Duke Compounding Facility with active pharmaceutical ingredient (Sochinaz SA, Switzerland, distributed by Bachem Americas, King of Prussia, Pennsylvania) plus dextrose as an inactive ingredient. Identical-looking placebo capsules contained dextrose. Each capsule contained zonisamide 100 mg or placebo, with patients and study staff blinded to contents. Dose was gradually titrated upward as follows: 1 capsule for 15 days, 2 during days 16-30, 3 capsules during days 31-45, and 4 from day 46 onward. The entire dose was taken at night. Blinded dose reduction was allowed and dose increase could be withheld. Patients had the option to discontinue the drug and remain in the study receiving only diet and lifestyle counseling.	Zonisamide 200 mg Dosing of matching placebo was identical.	Zonisamide 400 mg
Overall Study STARTED	74	76	75
Overall Study Completed Study While on Study Drug	54	51	62
Overall Study COMPLETED	71	73	74
Overall Study NOT COMPLETED	3	3	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Zonisamide for Weight Reduction in Obese Adults

Baseline characteristics by cohort

Measure	Placebo n=74 Participants	Zonisamide 200 mg n=76 Participants	Zonisamide 400 mg n=75 Participants	Total n=225 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	74 Participants n=5 Participants	76 Participants n=7 Participants	75 Participants n=5 Participants	225 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	43.5 years STANDARD_DEVIATION 10.3 • n=5 Participants	44.2 years STANDARD_DEVIATION 10.1 • n=7 Participants	42.3 years STANDARD_DEVIATION 10.0 • n=5 Participants	43.4 years STANDARD_DEVIATION 10.1 • n=4 Participants
Gender Female	44 Participants n=5 Participants	45 Participants n=7 Participants	45 Participants n=5 Participants	134 Participants n=4 Participants
Gender Male	30 Participants n=5 Participants	31 Participants n=7 Participants	30 Participants n=5 Participants	91 Participants n=4 Participants
Region of Enrollment United States	74 participants n=5 Participants	76 participants n=7 Participants	75 participants n=5 Participants	225 participants n=4 Participants

PRIMARY outcome

Timeframe: 1 year

Population: intent-to-treat

The primary endpoint was weight loss at 1-year, Month-12 weight minus baseline weight, in kilograms.

Outcome measures

Measure	Placebo n=74 Participants	Zonisamide 200 mg n=76 Participants	Zonisamide 400 mg n=75 Participants
Change in Body Weight	-4.0 kg Interval -5.8 to -2.3	-4.4 kg Interval -6.1 to -2.6	-7.3 kg Interval -9.0 to -5.6

SECONDARY outcome

Timeframe: 1 year

These were the proportions of patients losing 5% or more weight at 1-year relative to baseline. The measures were modeled with logistic regressions that included the three-level group proxy and a baseline weight covariate.

Outcome measures

Measure	Placebo n=74 Participants	Zonisamide 200 mg n=76 Participants	Zonisamide 400 mg n=75 Participants
Proportions of Patients With 5% Weight Loss	23 participants	26 participants	41 participants

SECONDARY outcome

Timeframe: 1 year

This outcomes measure followed the same principles at measurement of proportions of patients with 5% weight loss described elsewhere.

Outcome measures

Measure	Placebo n=74 Participants	Zonisamide 200 mg n=76 Participants	Zonisamide 400 mg n=75 Participants
Proportions of Patients With 10% Weight Loss	6 participants	17 participants	24 participants

SECONDARY outcome

Timeframe: 1 year

Population: intent-to-treat

Analyses was based on intent-to-treat ANCOVA. Difference scores from baseline to endpoint (Month-12) for each measure were regressed on the three-level proxy denoting group while controlling for the baseline value of the same measure. Contrasts were subsequently estimated in models, which had a significant overall treatment effect.

Outcome measures

Measure	Placebo n=74 Participants	Zonisamide 200 mg n=76 Participants	Zonisamide 400 mg n=75 Participants
Waist Circumference	-4.8 cm Interval -6.6 to -3.1	-6.1 cm Interval -7.8 to -4.3	-8.5 cm Interval -10.2 to -6.8

SECONDARY outcome

Timeframe: 1 year

Population: Participants who had CRP testing completed

C reactive Protein (CRP)

Outcome measures

Measure	Placebo n=73 Participants	Zonisamide 200 mg n=75 Participants	Zonisamide 400 mg n=75 Participants
Inflammatory Markers (CRP)	0.523 mg/L Standard Error 0.064	0.536 mg/L Standard Error 0.06	0.443 mg/L Standard Error 0.044

SECONDARY outcome

Timeframe: baseline, 1 year

Outcome measures

Measure	Placebo n=74 Participants	Zonisamide 200 mg n=76 Participants	Zonisamide 400 mg n=75 Participants
Change in Lipids Total Cholesterol	-1.9 mg/dL Interval -7.2 to 3.4	4.1 mg/dL Interval -1.0 to 9.2	-0.1 mg/dL Interval -5.0 to 4.9
Change in Lipids LDL Cholesterol	-2.0 mg/dL Interval -6.7 to 2.7	1.7 mg/dL Interval -2.8 to 6.3	-0.3 mg/dL Interval -4.7 to 4.1
Change in Lipids HDL Cholesterol	2.5 mg/dL Interval 0.7 to 4.3	1.5 mg/dL Interval -0.3 to 3.2	3.4 mg/dL Interval 1.7 to 5.1
Change in Lipids Triglycerides	-11.3 mg/dL Interval -22.6 to 0.0	0.7 mg/dL Interval -10.1 to 11.5	-11.7 mg/dL Interval -22.2 to -1.1

SECONDARY outcome

Timeframe: 1 year

Hospital Anxiety and Depression Scale - Depression (HADS-D) The HADS is a 14-item self-administered questionnaire that consists of 2 scales, one measuring anxiety (HADS-A), and the other measuring depression (HADS-D). Each subscale consists of 7 statements and the participant responds as to how each item applies to him/her over the past week on 4-point response scale. Separate scores are calculated for anxiety and depression and a score (ranging from 0 to 21) is obtained for each subscale. The higher the score, the more severe the anxiety or depression.

Outcome measures

Measure	Placebo n=74 Participants	Zonisamide 200 mg n=76 Participants	Zonisamide 400 mg n=75 Participants
Quality of Life as Measured by HADS_D	2.12 units on a scale Interval 1.54 to 2.7	2.76 units on a scale Interval 2.18 to 3.33	1.95 units on a scale Interval 1.38 to 2.53

SECONDARY outcome

Timeframe: Baseline, 1 year

Outcome measures

Measure	Placebo n=74 Participants	Zonisamide 200 mg n=76 Participants	Zonisamide 400 mg n=75 Participants
Change in Blood Pressure Systolic	-0.6 mm Hg Interval -2.9 to 1.6	-4.4 mm Hg Interval -6.7 to -2.1	-1.9 mm Hg Interval -4.1 to 0.4
Change in Blood Pressure Diastolic	-1.5 mm Hg Interval -3.2 to 0.1	-3.6 mm Hg Interval -5.3 to -2.0	-3.9 mm Hg Interval -5.5 to -2.3

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 30 other events

Deaths: 0 deaths

Zonisamide 200 mg

Serious events: 0 serious events

Other events: 37 other events

Deaths: 0 deaths

Zonisamide 400 mg

Serious events: 0 serious events

Other events: 39 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Placebo n=74 participants at risk	Zonisamide 200 mg n=76 participants at risk	Zonisamide 400 mg n=75 participants at risk
Gastrointestinal disorders Altered taste	0.00% 0/74 • 1-year	5.3% 4/76 • 1-year	5.3% 4/75 • 1-year
Gastrointestinal disorders Dry mouth	4.1% 3/74 • 1-year	6.6% 5/76 • 1-year	1.3% 1/75 • 1-year
Gastrointestinal disorders Nausea/vomiting	5.4% 4/74 • 1-year	5.3% 4/76 • 1-year	13.3% 10/75 • 1-year
Psychiatric disorders Anxiety related	2.7% 2/74 • 1-year	6.6% 5/76 • 1-year	9.3% 7/75 • 1-year
Psychiatric disorders Depression related	4.1% 3/74 • 1-year	3.9% 3/76 • 1-year	6.7% 5/75 • 1-year
Nervous system disorders Impaired concentration	1.4% 1/74 • 1-year	1.3% 1/76 • 1-year	5.3% 4/75 • 1-year
Nervous system disorders Impaired memory	1.4% 1/74 • 1-year	6.6% 5/76 • 1-year	10.7% 8/75 • 1-year
Nervous system disorders Headache	6.8% 5/74 • 1-year	10.5% 8/76 • 1-year	18.7% 14/75 • 1-year
Nervous system disorders Fatigue	2.7% 2/74 • 1-year	5.3% 4/76 • 1-year	9.3% 7/75 • 1-year
Nervous system disorders Somnolence	4.1% 3/74 • 1-year	11.8% 9/76 • 1-year	8.0% 6/75 • 1-year
Musculoskeletal and connective tissue disorders Musculoskeletal problems	12.2% 9/74 • 1-year	14.5% 11/76 • 1-year	10.7% 8/75 • 1-year

Additional Information

Kishore Gadde

Duke University Medical Center

Phone: 919-668-0208

Email: kishore.gadde@duke.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place