Revise Phase III Trial Protocol for Roflumilast Cream: CDSCO Panel Tells Sun Pharma

New Delhi: Following a thorough discussion on the proposed Phase III clinical trial protocol for roflumilast cream, the Subject Expert Committee (SEC) functional under the Central Drugs Standard Control Organization (CDSCO) has opined the drug major Sun Pharmaceuticals to modify the phase III protocol with respect to mentioning the toxic dose level for systemic absorption from the skin, number of participants, duration of the study, conditions for end of the treatment for the clearance/reduction of lesion, and etc.

This came after Sun Pharmaceuticals presented its proposal for the grant of permission to manufacture and marketing of Roflumilast cream 0.3% w/w with a Phase III clinical trial protocol for the proposed indication of an effective alternative for the treatment of plaque psoriasis, along with a bioequivalence (BE) study waiver.

Roflumilast is a selective phosphodiesterase-4 inhibitor indicated to decrease the risk of exacerbations in patients with severe chronic obstructive pulmonary disease (COPD) and to treat skin conditions such as plaque psoriasis and atopic dermatitis.

Roflumilast and its active metabolite (roflumilast N-oxide) are inhibitors of PDE4. Roflumilast and roflumilast N-oxide inhibition of PDE4 (a major cyclic 3′,5′-adenosine monophosphate (cyclic AMP) metabolizing enzyme) activity leads to accumulation of intracellular cyclic AMP. The specific mechanism(s) by which roflumilast exerts its therapeutic action are not well defined.

At the recent SEC meeting, the expert panel reviewed the proposal for the grant of permission to manufacture and marketing of Roflumilast cream 0.3% w/w with a Phase III clinical trial protocol for the proposed indication of an effective alternative for the treatment of plaque psoriasis, along with a bioequivalence (BE) study waiver.

The firm informed that the drug product Roflumilast cream 0.3% w/w is approved in Canada and the USA for the proposed indication.

After detailed deliberation, the committee recommended the following changes in the presented Phase III clinical trial protocol:

1. The toxic dose level for systemic absorption from the skin to be mentioned.

2. Power of the study to be increased to 95%; accordingly, the number of participants to be increased.

3. The duration of the study is to be increased to 12 weeks.

4. At least 50% of the Patients shall be followed up for 6 to 8 months after the end of the treatment for the clearance/reduction of the lesion.

5. At least 10% or (30 nos) of patients shall undergo biopsy testing with pathological opinion at the end of the follow-up study. Preferably biopsy study should also be done at baseline.

6. Photographic records of the measurement of the size of the lesion against the Ruler/scale shall be submitted as a part of CSR to verify the change in the colour/size of the lesions.