LYNX-1: Dim Light Vision Disturbance Phase 3 Clinical Trial for Nyxol

About the Trial

LYNX-1: Dim Light Vision Disturbance Phase 3 Clinical Trial for Nyxol (NCT04638660)

Randomized, Placebo-Controlled, Double-Masked Study of the Safety and Efficacy of Nyxol (0.75% Phentolamine Ophthalmic Solution) in Subjects with Dim Light Vision Disturbances

Detailed Info

This is a randomised, placebo-controlled, double-blinded, multi-centre, 2-part study to
assess the efficacy and safety of inhaled AZD1402. Part 1 will be performed in a lead-in
cohort for each dose level to evaluate the safety and pharmacokinetics (PK) in a population
with asthma controlled on medium dose inhaled corticosteroids (ICS)-long acting beta agonists
(LABA) before progressing to dosing in adults with asthma who are uncontrolled on medium dose
ICS-LABA in Part 2. The study will recruit participants receiving treatment with medium dose
ICS with LABA for Part 1 (separate inhalers or combination product) and medium dose ICS-LABA
as a combination product for Part 2 at Screening.

Part 2 will be initiated for each dose level following evaluation of safety and PK at the
relevant dose level in Part 1. The entire study period for each participant in both Parts 1
and 2, is approximately 3.5 months; a 2-week Screening Period, a 4 week Run-in Period, 4
weeks of Treatment Period, and 4 weeks of Follow-Up Period.

Study Phase

Phase 2

Estimated Enrollment

405

Estimated Primary Completion Date

April 7, 2022

Study Type

Interventional

Interventions
  • Drug: AZD1402
  • Drug: Placebo
  • Drug: Short acting beta agonist (SABA) (rescue medication)
  • Drug: Run-in medications (ICS-LABA combination)
Sponsor

AstraZeneca

Eligibility

Inclusion Criteria

  • Males or females ≥ 18 years of age
  • Subject-reported DLD (likely subjects with a history of multifocal IOLs, post-laser-assisted in situ keratomileusis [LASIK], corneal scars, and keratoconus)
  • Ability to comply with all protocol-mandated procedures independently and to attend all
  • Otherwise healthy and well-controlled subjects
  • Able and willing to give written consent to participate in this study
  • Able to self-administer study medication
  • PD ≥ 6 mm under mesopic conditions (prior to illumination) in at least one eye
  • ≤ 20 (20/100 Snellen or worse) Early Treatment Diabetic Retinopathy Study (ETDRS) letters in mLCVA score in at least one eye using the Precision Vision illuminated box with 5% translucent contrast chart and a mesopic filter at 4 m
  • ≥ 10 ETDRS letters (≥ 2 lines) improvement in mLCVA in at least one eye during illumination of the contralateral eye with a BAT system on the low setting using the Precision Vision illuminated box with 5% translucent contrast chart and a mesopic filter at 4 m

Exclusion Criteria

Ophthalmic:

  • Prior history of dry eye diagnosis, taking prescription drops for dry eye, or taking artificial tear drops occasionally for dry eye
  • Prior history of fluctuating vision
  • Clinically significant ocular disease as deemed by the Investigator that might interfere with the study
  • Known hypersensitivity to any topical alpha-adrenoceptor antagonists
  • Known allergy or contraindication to any component of the vehicle formulation
  • History of cauterization of the punctum or punctal plug (silicone or collagen) insertion or removal
  • Ocular trauma, ocular surgery (e.g., IOLs) or laser procedure (e.g., LASIK, photorefractive keratectomy [PRK]) within 6 months prior to screening
  • Use of any topical prescription or over-the-counter (OTC) ophthalmic medications of any kind (including artificial tear drops) within 7 days of screening until study completion, with the exception of lid scrubs with OTC products (e.g., OCuSOFT® lid scrub, SteriLid®, baby shampoo, etc.)
  • Recent or current evidence of ocular infection or inflammation in either eye. Subjects must be symptom free for at least 7 days.
  • History of diabetic retinopathy, diabetic macular edema, or dry or wet macular degeneration
  • History of any traumatic (surgical or nonsurgical) or nontraumatic condition affecting the pupil or iris
  • Unwilling or unable to discontinue use of contact lenses at screening until study completion, except for keratoconus subjects who may wear contacts up to 24 hours prior to their scheduled visits on Day 8 and Day 15
  • People with undiagnosed dry eye, at the determination of the Investigator. Dry eye evaluation should be based on one of the following dry eye tests:
    • TearLabs osmolarity test (> 308 mOsm/L in either eye or an inter-eye difference ≥ 10 mOsm/L)
    • Corneal fluorescein staining (> 1 grade in the inferior or central zone using the National Eye Institute scale)
    • Tear break-up time of < 10 seconds

Systemic:

  • Known hypersensitivity or contraindication to alpha- and/or beta-adrenoceptor antagonists
    • Predisposition to severe hypoglycemia (2 or more serious hypoglycemic episodes requiring assistance within the past year)
    • Any hospitalization or emergency room visit due to poor diabetic control within the past 6 months
    • Currently untreated diabetes mellitus or previously untreated subjects who initiated oral anti-diabetic medication or insulin within 3 months prior to Day 1
    • Any sign of diabetic retinopathy in either eye e. Uncontrolled diabetes mellitus defined by Hemoglobin A1c >12% taken within the last 3 months
  • Clinically significant systemic disease that might interfere with the study
  • Initiation of treatment with or any changes to the current dosage, drug, or regimen of any systemic adrenergic or cholinergic drugs within 7 days prior to screening or during the study
  • Participation in any investigational study within 30 days prior to screening and during the conduct of the study
  • Females of childbearing potential who are pregnant, nursing, planning a pregnancy, or not using a medically acceptable form of birth control
  • Resting HR outside the specified range (50-110 beats per minute)
  • Hypertension with resting diastolic BP > 105 mmHg or systolic BP > 160 mmHg