A Double-blind, Randomized Clinical Trial to Evaluate the Efficacy and Safety of Forskolin Eye Drops 1% in the Treatment of Open AngleGlaucoma – A Comparative Study

1. Pokhara University
School of Health and Allied Sciences
A Double-blind, Randomized Clinical Trial
to Evaluate the Efficacy and Safety
of Forskolin Eye Drops 1% in the
Treatment of Open Angle
Glaucoma – A Comparative Study
Presented By : Deepa kumari karn
Seminar 2nd , M Pharm (C.P), 1st Sem
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2. Pokhara University
School of Health and Allied Sciences
Table of Content
• Introduction
– Forskolin
– Open Angle Glaucoma
• Research Question
• Literature Review
• Objective
– General Objective
– Specific Objective
• Rational of Study
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• Methods
– Study design
– Participants
– Sample size
• Results
– Efficacy assessment
– Statistical Analysis
• Discussion
• Conclusion
• References
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Introduction
Forskolin
• It is labdane diterpene (17-β-acetoxy-8, 13-epoxy-1
α,6-β, 9 α -trihydroxylabd-14-en-11-one) obtained
from the roots of Coleus forskohlii an aromatic herb
• It has been extensively studied by many researchers
for IOP reduction and glaucoma treatment
• It is a potent noradrenergic stimulator of adenylate
cyclase, result of decreased intraocular pressure,
decreased inflow, and unchanged outflow facility
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Figure : Coleus forskohlii Figure : Structure of the forskolin

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Figure : Major parts of eye

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Figure: Open and closed angle glaucoma

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Open Angle Glaucoma
• Group of eye disease characterized by increased
intraocular pressure(>21 mmHg)
• Trabecular meshwork becomes less effective at
draining aqueous humor (intraocular pressure upto
45 to 50 mmHg)
• Typically, open angle glaucoma has no symptoms in
its early stages
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Figure: Effect of glaucoma

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Research Question
• Can the Forskolin Eye Drops 1% is efficacious and
Safe for the treatment of open Angle Glaucoma?
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Literature Review
• The various research suggests that the forskolin can
be used as an effective medication for heart disease,
hypertension, diabetes, asthma, decrease in the fasting
glucose levels, painful urination, insomnia, and
convulsions, weight loss therapy and so on.
• Forskolin acts primarily by activating the enzyme
adenylate cyclase, which results in increased cyclic
adenosine monophosphate (cAMP) in cells
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• Sear et al, reports the use of the forskolin has
nonadrenergic stimulator effect of the adenylate
cyclase that allowed a non invasive study in the
human eye of the effect of adenyl cyclase stimulator
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• P U Witte et al conducted a pilot double blind intra
individual comparison of Forskolin eye drops (0.3%-
0.6%-1.0% suspension) in 18 healthy male subjects
(6 per group) which demonstrated that Forskolin eye
drops (0.3%-0.6%-1.0%) lowers intraocular pressure
in healthy male subjects
• A randomised, double-blind, placebo--controlled,
cross-over design with forskolin eye drops (1.0%
suspension) revealed a highly significant maximum
reduction of 25% in IOP in 6 hours after instillation
of forskolin eye drops
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Objective
General Objective
• To evaluate the efficacy and safety of forskolin 1%
w/v aqueous solution for the treatment of open angle
glaucoma
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Specific Objective
 Assessment of the patient for the eligibility for the
inclusion for the research
 Measurement of intraocular pressure
Bring forskolin commercially into the market with
no or minimal side effects
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Rational of Study
• There are many drugs available for lowering IOP
acting through various mechanisms either alone or
as a combination for the treatment of glaucoma;
however, for adequate control of the IOP along with
the minimal side effects, new drugs are required
• Though a lot of research work has been carried on
Forskolin since 1980’s, none of the companies
commercialized it for treating IOP, for unknown
reasons
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Methods
Study design
• This study was a double-blind, controlled,
comparative, randomized, non cross over trial
• The clinical study was approved by the Drug
Controller General of India, New Delhi
• Trial was conducted in accordance with the Good
Clinical Practice guidelines and by adhering to all the
tenets of the Declaration of Helsinki
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Participants
• Inclusion criteria:-
– Adult male or female subjects having primary open angle
glaucoma
– Glaucoma with intraocular pressure of more than 24
mm/Hg
– No miotic or other therapy 24 hours before
– Off systemic therapy for glaucoma for at least four days
– Informed consent given
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• Exclusion criteria:-
– Subjects with conditions like secondary or closed angle
glaucoma, bronchial asthma, chronic obstructive
pulmonary disease, uncompensated cardiac failure,
pregnancy, sinus bradycardia or 2rd or 3rd degree atrio-
ventricular block
– Subjects, who have taken any inflammatory ophthalmic
dose in the past 3 months
– Subjects having concurrent drug intake e.g. β blockers,
diamox etc
– Pregnancy was also exclusion for this trial
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Sample size
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Results
Efficacy Assessments
• The tonometric recording for each eye at the
baseline visit for both the treatment groups were
recorded
• The tonometric recording for each eye at the each
visit for both the treatment groups were recorded
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Table: Intraocular pressure (mmHg) at baseline visit

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Table: Effect of treatment on intraocular pressure at every follow up visit

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Statistical Analysis
• The sample size was calculated for an alpha error of
0.05 and power at 90%
• For descriptive and demographic analysis, simple
statistical methods of mean, standard deviation were
used
• Two-way ANOVA test was employed for comparing
the results of decreased IOP trend in both the eyes
from visit 2 to last visit and between Forskolin and
Timolol group patients
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Discussion
• Intraocular pressure (IOP) is normally regulated by
changes in the volume of the aqueous humour
• Small variations in the production or outflow of
aqueous humour will have a large influence on the
intraocular pressure
• Forskolin and its analogues represent a new class of
drugs active against glaucoma yet differing in
molecular mechanism from that of any previously
used drug
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• In the present study with aqueous solution of 1%
Forskolin, it was observed the maximum IOP
reduction as 21.5%, achieved on day 28
• The results showed a decreased trend in IOP from
visit 2 through last visit between both the treatment
groups and the trend towards a decrease in
intraocular pressure was higher in the forskolin group
for both the eyes as compared to the timolol group;
which was statistically significant (p<0.05)
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Conclusion
• The results obtained demonstrate the efficacy of
1%w/v Forskolin (2 drops thrice a day) aqueous
solution in achieving fast onset of action and
uniformity of hypotensive activity
• Forskolin 1% w/v aqueous solution could be
recommended as a treatment of choice to Timolol
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Reference
• Majeed M, Nagabhushanam K, Natarajan S, Vaidayanathan P, Karri SK (2014) A
Double-blind, Randomized Clinical Trial to Evaluate the Efficacy and Safety of
Forskolin Eye Drops 1% in the Treatment of Open Angle Glaucoma – A
Comparative Study, Clinical Trial 4(5), 1-6.
• Joseph Caprioli MS, Larry Bausher, Douglas Gregory, and Alden Mead. Forskolin
Lowers Intraocular Pressure by Reducing Aqueous Inflow(1984), Investigative
Opthalmology and Visual Science 25,268-278
• M Rios, T Rujillo,(2014) Effect of Chronic Administration of Forskolin on
Glycemia and Oxidative Stress in Rats with and without Experimental Diabetes,
International Journal of Medical science11(5),448-452.
• Capioli J, Sears M, Bausaher L, Gregory D, Mead A(1984) Forskolin lowers
intraocular pressure by reducing aqueous inflow, Invest Opthalmol Vis Science 25,
268-277.
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Thank You
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