Phenylephrine “Not Significantly Different From” Placebo – Schering Study

Schering-Plough released a study on phenylephrine's efficacy as compared to pseudoephedrine and placebo Oct. 31 that "raises even more questions" about the drug, according to Rep. Henry Waxman (D-Calif.).

Results of the study, "The Decongestant Effect of Phenylephrine Compared with Placebo and Pseudoephedrine as Active Control in SAR Subjects Exposed to Pollen in the Vienna Challenge Chamber," show "phenylephrine was not significantly different from placebo in decreasing nasal congestion scores at any evaluation time."

In response, Waxman stated, "I hope FDA will now be convinced that it's time to conduct a serious scientific inquiry into whether these [phenylephrine] products actually work."

Waxman has asked FDA on several occasions to convene its Nonprescription Drugs Advisory Committee to discuss the efficacy of phenylephrine (¹ (Also see "Waxman Renews Push For FDA Examination Of Phenylephrine Efficacy" - Pink Sheet, 30 Oct, 2006.), p. 5).

FDA has responded that it will consider an NDAC meeting if "sufficient additional information" became available. In light of the new study results, the agency said it still has not determined whether a meeting will be held.

Alternatively, results of the Nov. 7 election could allow Waxman to convene a hearing on the topic himself. Because Democrats are now in the House majority, Waxman will likely become the Government Reform Committee chairman, where he is currently the ranking minority member.

Schering says its study demonstrates that "a single dose of 12 mg phenylephrine was not shown to be significantly superior to placebo in reducing nasal congestion scores from baseline."

The trial was a randomized, investigator-blind, placebo-controlled, three-way crossover study for 39 subjects with seasonal allergic rhinitis (SAR).

"The average first 6-hour post-baseline mean percent change from baseline in nasal congestion score was -7.1% for phenylephrine treatment compared with -2.2% for placebo treatment," the study finds.

However, the results showed a -27.1% post-baseline change for pseudoephedrine treatment, Schering says.

All three of the treatments were administered to each study subject in addition to pollen exposure, with a five-day washout period between each treatment visit, the company explains.

Schering states that the varying results achieved from different treatments could be attributed to the study's crossover design. Although PE demonstrated only 17% of the decongestant activity shown by PSE, the phase 1 difference between PE and placebo was 64% of the difference between PSE and placebo.

"It is hypothesized that crossover study designs that include PSE may not accurately reflect the treatment-effect sizes that would be seen if the study were run as a parallel-group design," Schering says.

That contention, however, is challenged by researcher Leslie Hendeles, who has studied the two drugs and intends to submit a citizen petition to FDA on the differences in their efficacy (² (Also see "Phenylephrine Efficacy Will Be Questioned In Citizen Petition" - Pink Sheet, 2 Oct, 2006.), p. 7).

"They made a statement that the order of the treatment decreased the effect of PE. That is, they are claiming that patients who received pseudoephedrine first had less of an effect when receiving PE second," Hendeles, who is with the University of Florida's Pharmacy Practice Department, said.

"Since there was a five-day washout between treatments, this is not possible," Hendeles told "The Tan Sheet."

Hendeles also noted the study's abstract "indicates that [Schering] measured nasal airway resistance but they did not provide the results."

That lack of disclosure is significant because "nasal airway resistance is a more robust endpoint and separates differences better than subjective symptom scores," he commented.

At least one other company is conducting a study on phenylephrine efficacy, FDA said. However, a spokesperson said the agency has not yet obtained the data because the firm is in the process of determining how and when to make the study results public.

Schering, which markets the pseudoephedrine-containing product Claritin-D , ran an ad campaign declaring it would not reformulate its product with phenylephrine in the wake of Combat Meth Act provisions (³ (Also see "Claritin-D “Staying Tough” Behind The Counter With Pseudoephedrine" - Pink Sheet, 2 Oct, 2006.), p. 8).

- Rebekah Moan