Study 2: CONQUER clinical trial

Overweight and obese patients with comorbidities achieved significant weight loss¹

QSYMIA (phentermine and topiramate extended-release) capsules CIV vs placebo for 1 year of treatment (P<0.0001)^1,2‡

2,487 overweight or obese patients (BMI 27 or greater and less than or equal to 45) with 2 or more weight-related comorbidities were evaluated¹
66% of patients in the Qsymia groups completed the trial vs 57% in the placebo group²
Most common reasons for discontinuation were withdrawal of consent (11.0%), loss to follow-up (10.2%), and adverse event (4.9%)²

Co-primary endpoints¹

Overall percent weight loss from baseline, ITT-LOCF analysis^‡
- 9.8% weight loss achieved by patients who took the top dose (15 mg/92 mg) of Qsymia and 7.8% for patients who took the recommended dose (7.5 mg/46 mg), compared with 1.2% in the placebo group (P<0.0001)¹
- 84% of patients responded to Qsymia who were randomized to the 7.5 mg/46 mg cohort. Responders were defined as patients who achieved at least 3% weight loss at 12 weeks^1,2
Within 8 weeks, patients achieved at least 5% weight loss, on average; these patients were randomized to Qsymia 7.5 mg/46 mg or 15 mg/92 mg¹
Patients achieving at least 5% weight loss at end of study
- 70% of patients who took the top dose (15 mg/92 mg) and 62% who took the recommended dose (7.5 mg/46 mg) achieved 5% or greater weight loss after 1 year vs 21% of those who took placebo (P<0.0001)¹
- 10% or greater weight loss was achieved by 48% and 37% of patients in the Qsymia groups vs 7% in the placebo group (P<0.0001)¹
- Patients randomized to Qsymia 7.5 mg/46 mg or 15 mg/92 mg achieved, on average, at least 5% weight loss within 8 weeks^1,2

Secondary metabolic parameters¹

STUDY 2—CONQUER: Treatment difference^§ from placebo in risk factors following 1 year of treatment¹

STUDY 2 (OVERWEIGHT AND OBESE WITH COMORBIDITIES)	PLACEBO (N=979)	Qsymia® 7.5 mg/46 mg (N=488)	Qsymia 15 mg/92 mg (N=981)	Qsymia 7.5 mg/46 mg	Qsymia 15 mg/92 mg
				Qsymia — Placebo: LS Mean
HEART RATE, BPM
BASELINE MEAN (SD)	72.1 (9.9)	72.2 (10.1)	72.6 (10.1)	+0.6	+1.7
LS MEAN CHANGE (SE)	-0.3 (0.3)	+0.3 (0.4)	+1.4 (0.3)	+0.6	+1.7
SYSTOLIC BLOOD PRESSURE, mmHg
BASELINE MEAN (SD)	128.9 (13.5)	128.5 (13.6)	127.9 (13.4)	-2.3	-3.2
LS MEAN CHANGE (SE)	-2.4 (0.48)	-4.7 (0.63)	-5.6 (0.5)	-2.3	-3.2
DIASTOLIC BLOOD PRESSURE, mmHg
BASELINE MEAN (SD)	81.1 (9.2)	80.6 (8.7)	80.2 (9.1)	-0.7	-1.1
LS MEAN CHANGE (SE)	-2.7 (0.3)	-3.4 (0.4)	-3.8 (0.3)	-0.7	-1.1
TOTAL CHOLESTEROL, %
BASELINE MEAN (SD)	205.8 (41.7)	201.0 (37.9)	205.4 (40.4)	-1.6	-3.0
LS MEAN CHANGE (SE)	-3.3 (0.5)	-4.9 (0.7)	-6.3 (0.5)	-1.6	-3.0
LDL-CHOLESTEROL, %
BASELINE MEAN (SD)	124.2 (36.2)	120.3 (33.7)	123.9 (35.6)	+0.4	-2.8
LS MEAN CHANGE (SE)	-4.1 (0.9)	-3.7 (1.1)	-6.9 (0.9)	+0.4	-2.8
HDL-CHOLESTEROL, %
BASELINE MEAN (SD)	48.9 (13.8)	48.5 (12.8)	49.1 (13.8)	+4.0	+5.6
LS MEAN CHANGE (SE)	+1.2 (0.7)	+5.2 (0.9)	+6.8 (0.7)	+4.0	+5.6
TRIGLYCERIDES, %
BASELINE MEAN (SD)	163.5 (76.3)	161.1 (72.2)	161.9 (73.4)	-13.3	-15.3
LS MEAN CHANGE (SE)	+4.7 (1.7)	-8.6 (2.2)	-10.6 (1.7)	-13.3	-15.3
FASTING INSULIN, QIU/mL
BASELINE MEAN (SD)	17.8 (13.2)	18.0 (12.9)	18.4 (17.5)	-4.2	-4.7
LS MEAN CHANGE (SE)	+0.7 (0.8)	-3.5 (1.1)	-4.0 (0.8)	-4.2	-4.7
FASTING GLUCOSE, mg/dL
BASELINE MEAN (SD)	106.6 (23.7)	106.2 (21.0)	105.7 (21.4)	-2.4	-3.6
LS MEAN CHANGE (SE)	+2.3 (0.6)	-0.1 (0.8)	-1.3 (0.6)	-2.4	-3.6
WAIST CIRCUMFERENCE, cm
BASELINE MEAN (SD)	113.4 (12.2)	112.7 (12.4)	113.2 (12.2)	-5.2^§	-6.8^§
LS MEAN CHANGE (SE)	-2.4 (0.3)	-7.6 (0.4)	-9.2 (0.3)	-5.2^§	-6.8^§

SD=standard deviation; SE=standard error. Least-squares (LS) mean. Study 1 adjusted for baseline body weight and diabetic status. ^§Statistically significant versus placebo based on the pre-specified method for controlling Type I error across multiple doses.

The effect of Qsymia (phentermine and topiramate extended-release) capsules CIV on cardiovascular morbidity and mortality has not been established¹
Among the 388 subjects with type 2 diabetes treated in study 2, reductions in HbA1c from baseline (6.8%) were 0.1% for placebo compared to 0.4% and 0.4% with Qsymia 7.5 mg/46 mg and Qsymia 15 mg/92 mg, respectively¹
Qsymia patients with Type 2 diabetes achieved an average HbA1c level below AACE- recommend HbA1c levels of 6.5%^1,11
Qsymia is not indicated for the treatment of hypertension, type 2 diabetes mellitus, stroke, or heart disease

Study design¹

Qsymia was specifically studied in overweight patients with comorbidities including:
- Hypertension: Elevated blood pressure (greater than or equal to 140/90 mmHg, or greater than or equal to 130/85 mmHg for diabetics) or requirement for greater than or equal to 2 antihypertensive medications
- High cholesterol: Triglycerides greater than 200-400 mg/dL or were receiving treatment with 2 or more lipid-lowering agents
- Diabetes: Elevated fasting blood glucose (greater than 100 mg/dL) or diabetes
- Waist circumference: 102 cm or greater in men, 88 cm or greater in women

At the beginning of the study, the average weight and BMI of patients was 227 pounds and 36.6 kg/m², respectively

For all patients, a well-balanced, reduced-calorie diet (decrease of 500 kcal/day) was recommended, and nutritional and lifestyle modification counseling was also offered

^‡Intent-to-treat, last observation carried forward

Additional clinical trial information

Study 1: EQUIP - Obese patients achieved significant weight loss

Proven weight loss at 12, 28 and 56 weeks^1,2

Qsymia is the only once-daily combination pill proven to significantly reduce weight — see the results over time and create a plan for your patients.^1-5

REVIEW THE CLINICAL DATA

Qsymia helps manage the intensity of hunger and cravings throughout the day¹

Learn about the release of the components of once-daily Qsymia.¹

HOW QSYMIA WORKS

Indication

Qsymia should be used together with a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index (BMI) of:

30 kg/m² or greater (obese) or
27 kg/m² or greater (overweight) in the presence of at least one weight-related medical condition such as high blood pressure, type 2 diabetes, or high cholesterol

LIMITATIONS OF USE:

The effect of Qsymia on cardiovascular morbidity and mortality has not been established
The safety and effectiveness of Qsymia in combination with other products intended for weight loss, including prescription and over-the-counter drugs, and herbal preparations, have not been established

Important Safety Information

Qsymia is contraindicated in pregnancy; in patients with glaucoma; in hyperthyroidism; in patients receiving treatment or within 14 days following treatment with monoamine oxidase inhibitors (MAOIs); or in patients with hypersensitivity or idiosyncrasy to sympathomimetic amines, topiramate, or any of the inactive ingredients in Qsymia.

Qsymia can cause fetal harm. Females of reproductive potential should have a negative pregnancy test before treatment and monthly thereafter and use effective contraception consistently during Qsymia therapy. If a patient becomes pregnant while taking Qsymia, treatment should be discontinued immediately, and the patient should be informed of the potential hazard to the fetus.

Qsymia can cause an increase in resting heart rate. Regular measurement of resting heart rate is recommended for all patients taking Qsymia, especially patients with cardiac or cerebrovascular disease or when initiating or increasing the dose of Qsymia. Qsymia has not been studied in patients with recent or unstable cardiac or cerebrovascular disease and therefore use is not recommended.

Topiramate, a component of Qsymia, increases the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior. Discontinue Qsymia in patients who experience suicidal thoughts or behaviors. Qsymia is not recommended in patients with a history of suicidal attempts or active suicidal ideation.

Acute angle closure glaucoma has been reported in patients treated with topiramate, a component of Qsymia. Symptoms include acute onset of decreased visual acuity and/or eye pain. Symptoms typically occur within 1 month of initiating treatment with topiramate but may occur at any time during therapy. The primary treatment to reverse symptoms is immediate discontinuation of Qsymia.

Qsymia can cause mood disorders, including depression, and anxiety, as well as insomnia. Qsymia can cause cognitive dysfunction (e.g., impairment of concentration/attention, difficulty with memory, and speech or language problems, particularly word-finding difficulties). Since Qsymia has the potential to impair cognitive function, patients should be cautioned about operating hazardous machinery, including automobiles.

Hyperchloremic, non-anion gap, metabolic acidosis has been reported in patients treated with Qsymia. If metabolic acidosis develops and persists, consideration should be given to reducing the dose or discontinuing Qsymia.

Qsymia can cause an increase in serum creatinine. If persistent elevations in creatinine occur while taking Qsymia, reduce the dose or discontinue Qsymia.

Weight loss may increase the risk of hypoglycemia in patients with type 2 diabetes mellitus treated with insulin and/or insulin secretagogues (e.g, sulfonylureas).

Qsymia has not been studied in combination with insulin. A reduction in the dose of antidiabetic medications which are non-glucose-dependent should be considered to mitigate the risk of hypoglycemia.

The most commonly observed side effects in controlled clinical studies, ≥5% and at least 1.5 times placebo, include paraesthesia, dizziness, dysgeusia, insomnia, constipation, and dry mouth.

To report negative side effects, contact VIVUS, Inc. at 1-888-998-4887 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please read the Qsymia Medication Guide and Full Prescribing Information.

This site is intended only for residents of the United States, its territories, and Puerto Rico.

*BMI (body mass index) measures the amount of fat in the body based on height and weight. BMI is measured in kg/m².
^†Or a BMI of 27 or more with one weight-related medical condition.

Site References

1. Qsymia Full Prescribing Information. Campbell, CA: VIVUS, Inc; 2017. 2. Data on file. VIVUS, Inc. 3. Belviq [package insert]. Woodcliff Lake, NJ: Eisai Inc; 2014. 4. Contrave [package insert]. La Jolla, CA: Orexigen Therapeutics, Inc; 2014. 5. Saxenda [package insert]. Plainsboro, NJ: Novo Nordisk Inc; 2015. 6. Hill AJ et al. Appetite. 1991;17(3):187-197. 7. Stubbs RJ et al. Physiol Behav. 2001;72(4):615-619. 8. Isaksson H et al. Food Nutr Res. 2008;52. 9. Pelchat ML. Appetite. 1997;28(2):103-113. 10. Hill AJ, Heaton-Brown L. J Psychosom Res. 1994;38(8):801-814. 11. Garber, AJ, Abrahamson MJ, Barzilay Jl, et al. AACE comprehensive diabetes management algorithm 2013. Endocr Pract. 2013; 19(2):327-336.

Study 2: CONQUER clinical trial

Overweight and obese patients with comorbidities achieved significant weight loss1

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QSYMIA (phentermine and topiramate extended-release) capsules CIV vs placebo for 1 year of treatment (P<0.0001)1,2‡

Co-primary endpoints1

Secondary metabolic parameters1

STUDY 2—CONQUER: Treatment difference§ from placebo in risk factors following 1 year of treatment1

Study design1