番茄社区

Overweight people who took the phentermine/topiramate combination diet drug Qsymia lost more weight than people taking a placebo or either drug alone in a study funded by Qsymia manufacturer VIVUS.

Over 28 weeks of treatment, the percentage of study participants who lost 10% or more of their body weight was 38.8% among those taking Qsymia 7.5/46 mg and 42% among those taking the 15/92 mg dose.

That compared with 6.8% of patients taking placebo, 12.5% taking phentermine 7.5 mg, 20.8% on phentermine 15 mg, 18.6% in patients taking topiramate ER 46 mg, and 23.8% in topiramate ER 92 mg patients.

After seven months, the mean percentage weight loss with either dose of Qsymia was significantly greater than with placebo (lower Qsymia dose; P<0.0001, higher dose; P<0.05) or the drug's individual components at all time points (P<0.05), researcher , of Weill Cornell Medical College in New York City, and colleagues, wrote in the journal

Study Considered by FDA

The study was conducted between December 2007 and September 2008 and submitted to the FDA as part of the drug's approval process.

The approval of Qsymia in mid July of 2012, within weeks of the greenlighting of Arena Pharmaceuticals' diet drug Belviq (lorcaserin HCI), ended a 13-year drought in the prescription weight-loss drug pipeline.

Qsymia was the first of the drugs to reach the market, but its , and phentermine monotherapy remains the most commonly prescribed weight-loss drug in the U.S.

In the study, researchers used a factorial design to compare the efficacy and safety of two marketed dosages of Qsymia (phentermine/topiramate 7.5/46 mg and 15/92 mg) with phentermine, topiramate ER, and placebo.

The trial initially included 756 obese adults with BMIs ranging from 30 to 45 kg/m^2.

The researchers examined seven treatment arms including placebo; two doses of phentermine monotherapy (7.5 mg and 15 mg), two doses of topiramate ER (46 mg and 92 mg) and two doses of the combination drug (7.5/46 mg and 15/92 mg).

The trial also incorporated an ancillary lifestyle intervention for all participants and included counseling to reduce energy intake by 500 kcal/day, to monitor calorie intake with a food diary, and to increase physical activity as tolerated.

Primary efficacy variables included weight loss percentage and the percentage of participants achieving at least 5% weight loss by week 28 in the intention-to-treat (ITT) population.

Other efficacy variables included absolute weight loss (in kg), percentage of participants achieving 10% or more weight loss, and changes in systolic and diastolic blood pressure, waist circumference, fasting glucose, HbA1c, and inflammatory biomarkers (adiponectin and high-sensitivity C-reactive protein [hsCRP]).

Adverse events were monitored at each visit and study participants who discontinued treatment were encouraged to continue with data assessments through study completion.

In addition to funding the research, VIVUS researchers participated in the initial design, data analysis, and reporting of the study.

Combo Drug More Effective at Lower Doses

The 7.5/46 mg Qsymia dosage group achieved statistically greater weight loss than was seen with the higher doses of phentermine and topiramate monotherapy. The higher Qsymia dose also induced greater weight loss than either placebo (P<0.05) or the combination's individual components at all time points (P<0.05).

This translated into an absolute weight loss of:

• 8.3 kg (18.3 pounds) in the lower-dose Qsymia group
• 9 kg (19.8 pounds) in the higher-dose Qsymia groups
• 1.5 kg (3.3 pounds) in the placebo group
• 5.3 kg (11.7 pounds) in the low-dose phentermine group
• 6 kg (13.2 pounds) in the high-dose phentermine group
• 4.7 kg (10.3 pounds) in the low-dose topiramate group
• 6.4 kg (14 pounds) in the higher-dose topiramate group

Treatment-emergent adverse events were mild to moderate in severity, but tended to be more frequent in the 15/92 mg Qsymia group than the other groups. The most common adverse events in the higher and lower dose Qsymia users included paresthesia (23% of Qsymia 15/92 patients, 16% of Qsymia 7.5/46 patients), dry mouth (18.5%, 13.2%), headache (15.7%, 15.1) and constipation (15.7%, 6.6%).

One participant in the higher-dose topiramate group experienced a heart arrhythmia, but the Qsymia users showed a decrease in heart rate.

"The 7.5/46 mg dose of Qsymia showed better efficacy than putting people on monotherapy with 15 mg of phentermine and 92 mg of topiramate," said Barbara Troupin, vice president for scientific communications and risk management at VIVUS.. "At this smaller dose, we don't see as many side effects."

There was also no evidence of new side effects associated with giving the two drugs in combination, she said.

Qsymia has been on the market since September of 2012, but the FDA initially restricted the drug's distribution to certified pharmacies and it was available only by mail until April of this year.

Docs Reluctant to Prescribe Diet Drugs

Troupin told 番茄社区 that early sales were sluggish because patients found it difficult to get the drug. It is now available in around 25,000 retail pharmacies across the country.

She added that while more patients are taking Qsymia, getting physicians to prescribe weight-loss drugs remains a challenge.

"It has been 13 years since a new obesity drug has come on the market," she said. "Clinicians are not in the habit of prescribing medications for obesity, but the AMA has declared obesity a disease and more attention is being paid to this issue."

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