1. Oral Administration of Gelesis100,
A Novel Hydrogel, Significantly
Decreases Body Weight in
Overweight and Obese Subjects
Arne Astrup1, MD, Mette Kristensen1, PhD, Lucio Gnessi2, MD, PhD, Mikiko Watanabe2, MD, PhD, Stepan Svacina3, MD,
Martin Matoulek3, MD, PhD, Pavol Hlubik4, MD, Hana Stritecka5, PhD, Franco Contaldo6, MD, PhD,
Fabrizio Pasanisi6, MD, PhD, Hassan M. Heshmati7, MD, Yishai Zohar7, Eyal S Ron7, PhD, Alessandro Sannino8, PhD,
Christian Demitri8, PhD, Cosimo Saponaro8.
1University of Copenhagen, Frederiksberg C, Denmark, 2Policlinico Umberto I, Rome, Italy, 3General Hospital in Prague, Prague, Czech Republic,
4Nutrition Disorder Center, Hradec Kralove, Czech Republic, 5Faculty of Military Health Sciences, Hradec Kralove, Czech Republic,
6Federico II University Hospital, Naples, Italy, 7Gelesis, Boston, MA, USA, 8Gelesis, Lecce, Italy.
INTRODUCTION
Overweight and obesity are
becoming major health problems
worldwide (1). The World Health
Organization estimated that the
worldwide prevalence of obesity has nearly
doubled between 1980 and 2008. In 2008,
approximately 500 million adults around the
globe were obese and it is projected that by
2015, this number will reach 700 million.
Overweight and obesity are responsible for in-creased
morbidity and mortality (2). Weight
loss of at least 5 to 10% appears to lower the
risk of many of the comorbidities (3).
The therapeutic benefit of all currently
avail-able anti-obesity tools is limited by
their marginal efficacy and variable
tolerability and safety profiles.
Gelesis100 is a novel, biocompatible hydrogel.
Gelesis100 is administered in capsules, each
containing thousands of tiny hydrogel particles
that when hydrated expand in the stomach and
mix with ingested foods. Gelesis100 increases
the volume and elasticity of the stomach and
small intestine contents, inducing satiety and
reducing caloric intake. Gelesis100 is composed
of two components which are used as food
ingredients, but when cross-linked, form a
unique structure that increases in volume
when hydrated. Gelesis100 does not create
one big mass, rather thousands of small indi-vidual
gel beads which have similar elasticity
(rigidity) as ingested foods, but without any
caloric value. Gelesis100 partially degrades in
the large intestine and loses its three dimen-sional
matrix structure and most of its absorp-tion
capacity. The water is absorbed from the
hydrogel back in the colon and Gelesis100 is
expelled in the feces.
A previous study in humans has shown that
single administration of 2 g of Gelesis100 sig-nificantly
increases the post-meal feeling of
satiety and decreases the feeling of hunger
before the subsequent meal (4).
OBJECTIVES
The aims of this study were to assess the ef-ficacy,
safety, and tolerability of chronic oral
administration of Gelesis100 in non-diabetic
overweight and obese subjects.
Body weight was the primary efficacy endpoint.
SUBJECTS
One hundred twenty-eight non-diabetic
overweight and obese subjects were studied
at five sites, in three European countries
(Denmark, Italy, and Czech Republic).

2. METHODS
Subjects were randomized to two Gelesis100
arms (2.25 g twice daily, n = 43 and 3.75 g
twice daily, n = 42) and a placebo/active com-parator
arm (n = 43). Treatment was adminis-tered
in capsules with 500 mL of water before
lunch and dinner, in a double-blind, parallel-group
fashion, over 12 weeks, in subjects on
hypocaloric diet (-600 kcal/day). The placebo/
active comparator capsule containedmicro-crystalline
cellulose, a fiber which is used as a
bulking agent.
For safety and tolerability, in addition to the
standard adverse event (AE) reporting, gas-trointestinal
symptoms that occurred during
the study were recorded through a question-naire
(solicited AEs).
Statistical analysis used analysis of covariance
model with baseline weight, gender, and
body mass index (BMI) as covariates, com-paring
Gelesis100 arms to placebo/active
comparator arm.
RESULTS
One hundred twenty-five subjects had at least
one post-baseline body weight assessment
(intention-to-treat “ITT” population) (Table 1).
One hundred ten subjects completed the
treatment.
One hundred twenty-six subjects provided
safety data (safety population).
In the ITT population, the mean (± SD) body
weight percent changes from baseline to the
end of treatment were -6.1 ± 5.1%, -4.5 ±
4.5%, and -4.1 ± 4.4%, with Gelesis100 2.25
g, Gelesis100 3.75 g, and placebo, respec-tively.
Weight loss was statistically significant
with Gelesis100 2.25 g (P = 0.026) (Figure 1).
Lower tolerability leading to lower compliance
may explain the observed efficacy result with
Gelesis100 3.75 g.
Subjects on Gelesis100 2.25 g had higher rate
of weight loss ≥ 10% and lower rate of weight
gain (Table 2).
The extent of weight loss was more pro-nounced
in subjects on Gelesis100 2.25 g with
fasting glucose > median at baseline (-8.2 ±
5.3%; P = 0.006) (Figure 2), especially in
those with impaired fasting glucose at baseline
(-10.9 ± 4.3%; P = 0.019) (Figure 3).
There was a significant negative correlation
between fasting glucose at baseline and change
in body weight in Gelesis100 2.25 g arm
(r = -0.50; P < 0.001) (Figure 4) contrasting with
a lack of significant correlation in Gelesis100
3.75 g arm (r = -0.01; P = 0.968) and placebo
arm (r = -0.06; P = 0.708) (Figure 5).
Treatment with Gelesis100 was safe and well
tolerated. The most common AEs were of gas-trointestinal
origin and included bloating, flat-ulence,
abdominal pain, and diarrhea, with
lower prevalence in Gelesis100 2.25 g arm
compared to placebo and Gelesis100 3.75 g
arms (Table 3). The most common non-gastro-intestinal
AEs were common cold and headache.
Serious AEs (SAEs) were observed in 3 subjects
on placebo (gallstone and abdominal pain).
The AEs were usually of mild intensity, occurred
at different times during the course of the study,
and resolved within 1 week in most cases.
Dropout after randomization occurred in 2 sub-jects
(5%) on Gelesis100 2.25 g, 10 subjects
(24%) on Gelesis100 3.75 g, and 9 subjects
(21%) on placebo. No AE was responsible for
the dropout with Gelesis100 2.25 g.
CONCLUSION
Chronic administration of Gelesis100 (2.25 g
twice daily) to overweight and obese sub-jects
significantly decreases the body weight.
Weight loss is especially dramatic in subjects
with impaired fasting glucose at baseline (pre-diabetic
subjects). The treatment is safe and
well tolerated.
Through its first-in-class, mechanical, and
non-invasive approach, Gelesis100, as a med-ical
device, is a product that is well-positioned
to overcome the limitations of the current
weight-loss tools and fulfill the overwhelming
unmet medical need for a safe and effective
weight-loss product in overweight and obese
subjects, especially in those with prediabetes.
If confirmed in subsequent studies, Gelesis100
also has the potential to induce dramatic
weight loss in overweight and obese subjects
with type 2 diabetes.

3. Table 1. General characteristics of the ITT population at baseline .
Parameter Gelesis100
2.25 g
(n = 42)
Gelesis100
3.75 g
(n = 41)
Placebo
(n = 42)
Male (n) 13 (31%) 14 (34%) 13 (31%)
Female (n) 29 (69%) 27 (66%) 29 (69%)
Age (years)* 42.4 ± 12.3 46.1 ± 11.2 44.0 ± 11.7
BMI* 31.2 ± 2.3 31.8 ± 2.5 32.0 ± 2.3
Overweight (n) 14 (33%) 12 (29%) 12 (29%)
Obese (n) 28 (67%) 29 (71%) 30 (71%)
Glucose (mmol/L)*
Glucose (mg/dL)*
5.18 ± 0.54
93 ± 10
5.20 ± 0.50
94 ± 9
5.31 ± 0.58
96 ± 10
*Mean ± SD.
Table 2. Body weight response in the ITT population .
Parameter Gelesis100
2.25 g
(n = 42)
Gelesis100
3.75 g
(n = 41)
Placebo
(n = 42)
Weight gain 3 (7%) 9 (22%) 7 (17%)
Weight loss < 5% 21 (50%) 13 (32%) 18 (43%)
Weight loss ≥ 5% 18 (43%) 19 (46%) 17 (40%)
Weight loss ≥ 10% 11 (26%) 5 (12%) 5 (12%)
Table 3. Gastrointestinal AE s* in the safety population .
Parameter Gelesis100
2.25 g
(n = 42)
Gelesis100
3.75 g
(n = 41)
Placebo
(n = 43)
Any AE 31 (74%) 35 (85%) 36 (84%)
Any gastrointestinal AE 25 (60%) 31 (76%) 32 (74%)
Bloating 12 (29%) 15 (37%) 16 (37%)
Flatulence 11 (26%) 15 (37%) 13 (30%)
Abdominal pain 9 (21%) 12 (29%) 15 (35%)
Diarrhea 8 (19%) 10 (24%) 16 (37%)
*Gastrointestinal AEs were solicited and recorded through a questionnaire.

4. Figure 1. Body weight (% change from baseline, mean
± SEM) in ITT population.
Figure 2. Body weight (% change from baseline, mean
± SEM) in ITT population with fasting glucose > median
(5.15 mmol/L or 93 mg/dL) at baseline.
Figure 3. Body weight (% change from baseline, mean
± SEM) in ITT population with impaired fasting glucose
(5.60 to < 7.00 mmol/L or 100 to < 126 mg/dL) at baseline.
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Figure 4. Correlation between fasting glucose at baseline
(mmol/L) and body weight change from baseline (%) in
ITT population on Gelesis100 2.25 g.
Figure 5. Correlation between fasting glucose at baseline
(mmol/L) and body weight change from baseline (%) in
ITT population on placebo.
The content of this document was presented in a Poster at the ICE/ENDO 2014 Meeting, Chicago, Illinois, June 21-24, 2014.