Clinical Trial Finds Weight Loss Through An Experimental Drug

Clinical Trial Finds Weight Loss Through An Experimental DrugClinical Trial Finds Weight Loss Through An Experimental Drug: Researchers at Duke University Medical Center have found that an investigational combination of drugs that are used to treat epilepsy, migraine and obesity is producing a 10 percent weight loss in patients who were suffering from obesity during a one-year clinical trial.

The treatment was also helpful in other health areas as well. For example, the controlled-release combination therapy, which consists of topiramate and phentermine were also helpful in decreasing blood pressure and hemoglobin A1C levels. Cholesterol, triglycerides and inflammatory markers were also improved during the clinical trial.

“Patients receiving this combination experienced 8.6 percent greater weight loss, on average, compared to those patients receiving placebo,” stated Kishore M. Gadde, M.D., director of Duke’s obesity clinical trials program. “This kind of weight loss, coupled with significant reductions in cardiometabolic risk factors represents a potentially important advancement in the management of obesity.”

Presently, the only drug available for long-term obesity is Orlistat. Orlistat is available over-the-counter known as Alli, and in a prescription strength known as Xenical. During studies, Orlistat, used at its maximum strength has shown a seven pound weight loss over placebos.

“The combination drug achieves about 19 pounds of weight loss relative to placebo at one year,” Gadde says.

During the 56-week trial, 3 studies were conducted in 93 U.S. Centers with more than 2400 patients who all had a BMI of 27-45 kg/m2 and who also had two or more health issues such as heart disease or diabetes. The patients were randomly drawn to either receive either one/two low-dose drug combinations or a placebo. The drugs used in the trial were phentermine, which has been available for treatment of short-term obesity since 1959, and topirmate, which is also known as Topamax. The patients in this study were also offered advice about exercise and diet.

Vivus funded this clinical trial who is also trying to get Qnexa, the name of the combination therapy to be approved by the FDA.  It was first declined in October 2010 because the FDA ruled that the drug could not be approved in its current form. The FDA needed more safety data about the drug. In March of 2011, a warming was issued by the FDA stating that women who were pregnant and taking topirmate were more at risk for having babies that were born with cleft palate or cleft lip. The drug has also been associated with depression, anxiety, mood changes, and memory problems.

During the Qnexa clinical trials, 34 women became pregnant. Gadde states that, “No birth defects were reported for the babies born.” Gadde also stated, “There is no reason for women to use weight loss drugs while they are pregnant or trying to become pregnant.”

Broken down, the study used once-daily doses of the combined drugs listed below.

Phentermine 7.5mg plus Topiramate CR 46mg achieved 7.8 percent weight loss (p<0.0001 vs. placebo).

Phentermine 15mg plus topiramate CR 92mg achieved 9.8 percent weight loss (p<0.0001 vs. placebo). The placebo group experienced 1.2 percent weight loss.

The highest advance in cardiovascular disease and diabetes were seen in high-risk patients among the groups given placebo, phentermine 7.5mg plus topiramate 40mg, or phentermine 15mg plus topiramate 92mg individually:

  • Systolic blood pressure: -4.9mmHg, -6.9mmHg, -9.1mmHg
  • Diastolic blood pressure: -3.9mmHg, -5.2mmHg, -5.8mmHg
  • Total cholesterol: -4.9%, -5.7%, -7.8%
  • LDL: -3.6%, 0.7%, -4.3%
  • HDL: 2.8%, 9.5%, 10.7%
  • Triglycerides: -8.8%, -24.1%, -25.6%
  • Hemoglobin A1C in diabetics: -0.1%, -0.4%, -0.4%
  • Fasting insulin in pre-diabetics: 6.0pmol/L, -29.2pmol/L, -31.9pmol/LM

The most common side effects in the groups given placebo, phentermine 7.5mg plus topiramate 40mg, or phentermine 15mg plus topiramate 92mg, individually were:

  • Dry mouth (2%, 13% and 21%)
  • Parethesia (numbness or tingling), (2%, 14%, 21%)
  • Constipation (6%, 15%, 17%)
  • Insomnia (5%, 6%, 10%)
  • Dizziness (3%, 7%, 10%)
  • Dysgeusia (distorted sense of taste) (1%, 7%, 10%)

“Although the overall incidence of these events was relatively small,” Gadde says, “clearly there is a dose-related increase in risk.”

“Two thirds of Americans are overweight or obese. For obese patients who have failed to achieve meaningful weight loss with diet and exercise, we have just one treatment before jumping to bariatric surgery. We need more treatment options.”