Efficacy and Safety of NT 201 in the Treatment of Lateral Periorbital Wrinkles

• Response assessed by the investigator at maximum smile for either eye area compared to baseline. [ Time Frame: Weeks 2, 4, 12, and 20 ] [ Designated as safety issue: No ]
  Responder: subjects with improvement of at least 1 point on a 4 point scale for lateral periorbital wrinkles.
• Response assessed by the subject's global assessment at maximum smile for either eye area compared to baseline. [ Time Frame: Weeks 2, 4, 12, and 20 ] [ Designated as safety issue: No ]
  Responder: subjects with at least a moderate improvement, i.e. a score of at least +2 on a 9 point Likert scale.

To investigate the efficacy and safety of incobotulinumtoxinA (Xeomin) in comparison to placebo in the treatment of moderate to severe lateral periorbital wrinkles at maximum smile and to compare two different application schemes of Xeomin. Each subject will be treated on the right and left eye area, using the same dose but different application schemes (i.e. 3 or 4 injection sites).

Conducted in Europe

• Drug: IncobotulinumtoxinA (Xeomin)
  Intramuscular injection at day 0, at 3 and 4 injection sites per eye (4 x 3 or 3 x 4 units = 12 units per eye)
• Drug: Placebo
  Intramuscular injection at day 0, at 3 and 4 injection sites per eye.

• Experimental: IncobutolinumtoxinA (Xeomin), 4-injection scheme

  IncobotulinumtoxinA (Xeomin), also known as 'NT 201' or 'Botulinum toxin type A (150kD), free of complexing proteins' (active ingredient:

  Clostridium Botulinum neurotoxin Type A free of complexing proteins) powder for solution for injection; dose: one injection session of solution, prepared by reconstitution of powder with 0.9% sodium chloride (NaCl); total volume 0.24 mL per side, i.e. 4 x 0.06 mL (4 x 3 units = 12 units); mode of administration: intramuscular injection.

  Intervention: Drug: IncobotulinumtoxinA (Xeomin)
• Placebo Comparator: Placebo 4-injection scheme
  Placebo to IncobotulinumtoxinA (Xeomin) powder for solution for injection; dose: one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl; total volume 0.24 mL per side, i.e. 4 x 0.06 mL placebo solution; mode of administration: intramuscular injection.
  Intervention: Drug: Placebo
• Experimental: IncobotulinumtoxinA (Xeomin), 3-injection scheme

  IncobotulinumtoxinA (Xeomin), also known as 'NT 201' or 'Botulinum toxin type A (150kD), free of complexing proteins' (active ingredient:

  Clostridium Botulinum neurotoxin Type A free of complexing proteins) powder for solution for injection; dose: one injection session of solution, prepared by reconstitution of powder with 0.9% sodium chloride (NaCl); total volume 0.24 mL per side, i.e. 3 x 0.08 mL (3 x 4 units = 12 units); Mode of administration: intramuscular injection.

  Intervention: Drug: IncobotulinumtoxinA (Xeomin)
• Placebo Comparator: Placebo 3-injection Scheme
  Placebo to IncobotulinumtoxinA (Xeomin) powder for solution for injection; dose: one injection session of solution, prepared by reconstitution of powder with 0.9% NaCl; total volume 0.24 mL per side, i.e. 3 x 0.08 mL placebo solution; mode of administration: intramuscular injection.
  Intervention: Drug: Placebo

Main Inclusion Criteria:

- Moderate (grade 2) to severe (grade 3) symmetrical lateral periorbital wrinkles assessed by the investigator according to the 4-point scale at maximum smile

Main Exclusion Criteria:

- Significant facial asymmetry