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A randomized, participant- and investigator-masked, vehicle-controlled study to assess the safety, tolerability and pharmacokinetics of topical ocular SAF312 in Japanese healthy participants

Safety, tolerability and pharmacokinetics study of topical ocular SAF312 in Japanese healthy participants

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For all analysis sets, participants were analyzed according to the study treatments received. The all participants were healthy adult Japanese. - Part 1: Majority of the participants were females (62.5%). The mean age of the participants was 27.8 (7.52) years with mean BMI of 21.59 (1.634) kg/m2 - Part 2: Majority of participants were females (62.5%). The mean age of the participants was 29.6 (7.93) years with mean BMI of 21.99 (1.892) kg/m2 - Part 3: Majority of the participants were males (66.7%). The mean age of the participants was 33.7 (8.73) years with mean BMI of 22.03 (2.251) kg/m2

Each Cohort in the Part 1 and Part 2 portions of the study consisted of 8 participants of which 2 were randomized to receive vehicle and 6 were randomized to receive SAF312. Part 3 consisted of 12 participants randomized in a 3-way crossover (Latin square design) who received SAF312, vehicle and oxybuprocaine in three different sequences. Two participants discontinued the study after treatment, one in Part 2 and another in Part 3. The discontinuations are not safety related.

- No deaths, serious adverse events (SAEs) and adverse events (AEs) that led to discontinuation of study treatment were observed in any part of the study. - No ocular AEs were reported in this study. - No AEs were observed in the Part 1. - A total of 2 AEs were observed in 2 participants (25.0%) one each in SAF312 1.5% (16.7%) and vehicle (50.0%) treatment groups in part 2 and both were mild in intensity. Both AEs were not suspected to be related to the study drug by the Investigator. - Only 1 AE was observed in 1 participant (8.3%) after receiving vehicle in Part 3. It was mild in intensity and was not suspected to be related to the study drug.

Primary outcome measures - - No deaths, serious adverse events (SAEs) and adverse events (AEs) that led to discontinuation of study treatment were observed in any part of the study. - No AEs related to the study treatment were reported in this study. - No ocular AEs were reported in this study. - No AEs were observed in the Part 1. - A total of 2 AEs were observed in 2 participants (25.0%) one each in SAF312 1.5% (16.7%) and vehicle (50.0%) treatment groups in part 2 and both were mild in intensity. Both AEs were not suspected to be related to the study drug by the Investigator. - Only 1 AE was observed in 1 participant (8.3%) after receiving vehicle in Part 3. It was mild in intensity and was not suspected to be related to the study drug. Secondary outcome measures - Increase in dose from 0.5% to 1.5% resulted dose-proportional increase in systemic exposure, and with low systemic exposure of one eye drop SAF312 1.5% 4 times daily for 7 days in healthy Japanese participants.

In conclusion, topical ocular SAF312 was well tolerated with no ocular and systemic safety and tolerability concerns. Increase in dose from 0.5% to 1.5% resulted dose-proportional increase in systemic exposure, with low systemic exposure of one eye drop SAF312 1.5% 4 times daily for 7 days in healthy Japanese participants.

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2031210588

Hiroyuki Yamada

Novartis Pharma. K.K.

Toranomon Hills Mori Tower 23-1, Toranomon 1-chome Minato-ku, Tokyo 105-6333, Japan

rinshoshiken.toroku@novartis.com

Hiroyuki Yamada

Novartis Pharma. K.K.

Toranomon Hills Mori Tower 23-1, Toranomon 1-chome Minato-ku, Tokyo 105-6333, Japan

+81-120-003-293

rinshoshiken.toroku@novartis.com

Complete

Feb. 01, 2022

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

other

- Written informed consent must be obtained before any assessment is performed
- Japanese healthy male and female participants of age 20 to 45 years (inclusive), and in good health as determined by past medical history, physical examination, vital signs, electrocardiogram(ECG), and laboratory tests at screening
- At screening, participants must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) within the range of 18 - 30 kg/m2. BMI = Body weight(kg) / [Height (m)]2
- At screening, vital signs (body temperature, systolic and diastolic blood pressure(BP) and pulse rate) will be assessed in the sitting position. Sitting vital signs should be within the following ranges:
- body temperature between 35.0-37.5 degree Celsius
- systolic BP, 90-139 mmHg
- diastolic BP, 50-89 mmHg
- pulse rate, 40-90 bpm
If vital signs are outside these ranges, the Investigator may obtain two additional readings, so that up to three consecutive assessments are made. At least the last reading must be within the ranges provided above in order for the participant to qualify.
- Able to communicate well with the investigator, to understand and comply with the requirements of the study
- For Part 3, participants should have baseline levels of eye sensitivity in the range of 50 to 60 mm (inclusive) as measured by the Cochet-Bonnet type esthesiometer at screening.

- Participants demonstrating any medical condition (systemic or ophthalmic) that may, in the opinion of the investigator, and based on the content of the Investigator's Brochure(IB), preclude the safe administration of test article or safe participation in this study
- History of any ocular surgery or laser within the past 6 months prior to screening
- History of any chronic eye disease other than refractive error, incipient cataract, strabismic amblyopia, or anisometropic amblyopia
- Participants with a history of acute eye disease (such as infection, corneal abrasion, or allergy) within the past 6 months from screening may be eligible if the disease is not currently active
- Any currently active ocular condition that requires use of topical eye drops
- Participants using CPAP or other sleep apnea devices
- Part 3 (esthesiometry) only, participants who have used contact lenses in the past 3 years or currently, in order to minimize variability in cornea sensitivity because of contact lens use

Both

corneal induced chronic pain

Part 1 cohort 1 : Single drop of 0.5% SAF312 vs. vehicle
Part 1 cohort 2 : Single drop of 1.5% SAF312 vs. vehicle
Part 2 : 1.5% SAF312 Single drop q.i.d. x 7 days vs. vehicle
Part 3 : 3x3 Latin square design for Single drop of 1.5% SAF312 vs. vehicle vs. Oxybuprocaine 0.4% Hydrochloride ophthalmic solution

- All safety endpoints (including adverse events, vital signs, ECG, safety laboratory)
- Ocular safety endpoints (BCVA, IOP, slit lamp biomicroscopy, corneal staining, dilated fundus
exam)
- Time to hand withdrawal in hand immersion test (in Part 2 only)

+81-3-6665-0572

Jan. 25, 2022

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