-
Toujeo® provides a
flatter profile than insulin degludec
with less within-day
fluctuations -
PARIS, Nov. 11, 2016 /CNW/ - Sanofi presented today the
full results of a pharmacokinetic / pharmacodynamic (PK/PD) study
with Toujeo® (insulin glargine 300 Units/mL) and insulin
degludec 100 Units/mL (Deg-100) at the 16th Annual
Diabetes Technology Meeting, Bethesda,
Maryland, U.S.[1]
In patients with type 1 diabetes, the Toujeo® PK/PD
profile at a clinically relevant dose (0.4 U/kg/day, the average
dose used in worldwide clinical
practice)[2] was flatter and more
evenly distributed over 24 hours compared with the profile of
insulin degludec. The within-day fluctuation of metabolic activity
was 20% lower (p=0.047) for Toujeo® than insulin
degludec.
An overall flat PK/PD profile and an evenly distributed exposure
over 24 hours were observed for Toujeo® at both dose levels studied
(0.4 and 0.6 U/kg/day).
"These new findings may have clinical implications for people
with type 1 diabetes on basal insulin therapy," said Dr.
Timothy Bailey, Clinical Associate
Professor, University of California, San
Diego. "Toujeo® has already shown an improved
PK/PD profile when compared to insulin glargine 100 Units/mL
(Gla-100), with a flatter profile. Also in a previous CGM
study[3] in adults with type 1
diabetes versus Gla-100, Toujeo showed less between-day variability
and less within-day fluctuations, associated with a lower risk of
nocturnal confirmed (≤54 mg/dL) or severe hypoglycemia in the first
8 weeks.[3] The results observed
in the current PK/PD study comparing Toujeo® versus
Deg-100 confirm that Toujeo has an interesting profile with the
potential to help the people with diabetes to reach their targets
with less risk of hypoglycemia."
"In this PK/PD study, we observed a more favorable profile for
Toujeo® compared to insulin degludec," said Riccardo Perfetti, Head of Global Diabetes
Medical Team, Sanofi. "The clinical implications of these findings
are currently being investigated."
About Toujeo® PK/PD
study (LPS14585)[1]
Rationale:
Although basal insulin injections cannot perfectly replicate
endogenous insulin production, the 'ideal' basal insulin for
diabetes therapy would have stable pharmacodynamic (PD) and
pharmacokinetic (PK) profiles. Smaller and less variable glucose
excursions may result in more predictable 24hour profiles and less
hypoglycemia, and could translate into an improved experience for
people on basal insulin and better adherence to therapy.
Study design:
This was a randomized, double-blind, 2x2, crossover,
euglycemic-clamp study in two parallel cohorts of people with type
1 diabetes (48 people in total) to compare the pharmacodynamic and
pharmacokinetic properties of 0.4 and 0.6 U/kg/day insulin glargine
300 Units/mL (Toujeo®, Gla-300) with the same dose
levels of insulin degludec 100 Units/mL (Deg-100) in steady state
after 8 days multiple dosing regimen.
Key results:
Pharmacodynamics:
Within-day fluctuation of the smoothed glucose infusion rate
(GIR-smFL0-24) was significantly lower with Gla-300 versus Deg-100
at the 0.4 U/kg dose level. At the 0.4 U/kg dose level, relative
6-hour fractions of GIR-AUC0-24 were more evenly distributed with
Gla-300 versus Deg-100. GIR-smFL0-24 and 6-hour fractions of
GIR-AUC0-24 were similar between insulins at the supra-therapeutic
0.6 U/kg dose level. At both dose levels, GIR-AUC0-24 and GIRmax
were lower for Gla-300 versus Deg-100, while T50%-GIR-AUC0-24 and
duration of BG control were similar foreach insulin.
Pharmacokinetics:
Both dose levels of Gla-300 provided plateau-like insulin
profiles up to 16 hours post-dose, followed by a subsequent slow
decline. For Deg-100, insulin increased at both dose levels from
the time of injection until ~10 hours after dosing, with subsequent
slow decline. Exposure of both insulins was measurable until clamp
end (30 hours). At both dose levels the 6-hour fractions of
INS-AUC0-24 were more evenly distributed with Gla-300 versus
Deg-100.
About Toujeo® CGM
study[3]
Rationale:
Continuous glucose monitoring (CGM), is a valuable way to
confirm whether the differences observed in the PK and PD
properties of insulins under experimental condition translate to
clinically relevant differences in their 24-hour glucose profiles
and other parameters of glycemic control, including
hypoglycemia.
Study design:
This was a multicenter, 16-week, open-label, Phase II,
parallel-group, two-period crossover study including 59 people with
type 1 diabetes (PDY12777; NCT01658579). The primary endpoint was
the mean percentage of time within the glucose range of 4.4-7.8
mmol/L (80-140 mg/dL) during the last 2 weeks of treatment in each
treatment period (Weeks 7-8 and Weeks 15-16). The main secondary
endpoints were the average 24-hour glucose profiles based on CGM
(mmol/L) for the last 2 weeks of treatment in each treatment period
and the incidence of participants experiencing at least one
hypoglycemic event (defined by American Diabetes Association
criteria) in either study period.
Key results:
The percentage of time within the glucose range of 4.4-7.8
mmol/L (primary endpoint) was similar for participants receiving
Gla-300 vs Gla-100 (LS mean difference 0.75%, p=0.73). Average
24-hour glucose profiles showed a more constant glucose level with
Gla-300 vs. Gla-100.
About Toujeo®
Toujeo® is a once-daily basal insulin based on a
broadly-used molecule (insulin glargine). Toujeo has been approved
by the U.S. Food and Drug Administration (FDA), the European
Commission, Health Canada, the Therapeutic Goods Administration in
Australia, and the MHLW in
Japan (where its approved brand
name is Lantus® XR), and is under review by other
regulatory authorities around the world.
About Sanofi
Sanofi, a global healthcare leader, discovers, develops and
distributes therapeutic solutions focused on patients' needs.
Sanofi is organized into five global business units: Diabetes and
Cardiovascular, General Medicines and Emerging Markets, Sanofi
Genzyme, Sanofi Pasteur and Merial.
References:
- Bailey T, et al. Insulin Glargine 300 U/mL (Gla-300) Provides
More Stable and More Evenly Distributed Steady-state PK/PD Profiles
Compared with Insulin Degludec in Type 1 Diabetes. Poster presented
at Diabetes Technology Meeting, November 11,
2016
- Data on file, Adelphi Real World Diabetes DSP XII, 2015.
- Bergenstal RM, et al. Diabetes Technol Ther
2015;17(S1):16 (Abstract 39)
SOURCE SANOFI