The purpose of this study is to investigate how quickly and to what extent PF-06882961 is absorbed and eliminated from the body. The study will also investigate how safe the new compound PF-06882961 is and how well it is tolerated when it is…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Total recovery of radioactivity in urine and feces, and both routes combined,
expressed as a percent of total oral radioactive dose administered.
Secondary outcome
Metabolic profiling/identification and determination of relative abundance of
[14C]PF-06882961 and the metabolites of [14C]PF-06882961 in plasma, urine, and
feces.
AUClast, AUCinf, maximum concentration (Cmax), time of maximum concentration
(Tmax), and plasma elimination half-life (t*) to describe single oral dose PK
of:
* Total radioactivity in plasma;
* PF-06882961 in plasma.
Parameters to describe intravenous plasma PK: AUClast, AUCinf, t*, MRT, CL &
Vss.
Absolute oral bioavailability (F) computed from plasma AUCinf of oral unlabeled
PF-06882961 in Period 2 and intravenous microtracer of [14C]PF-06882961 in
Period 2.
Fraction absorbed calculated from ratio of total urinary radioactivity
following oral administration of [14C]PF-06882961 in Period 1 and intravenous
administration of [14C]PF-06882961 in Period 2.
Safety endpoints including physical examinations, adverse events, clinical
laboratory measurements, vital signs, and ECG.
Background summary
PF-06882961 is a new investigational compound that may potentially be used for
the treatment of Type-2 Diabetes Mellitus (T2DM).
T2DM is characterized by insulin resistance, a disorder in which cells do not
respond effectively to insulin, resulting in higher blood glucose levels. While
existing treatment of diabetes may provide satisfactory blood glucose control
for some patients, there remains a large number of patients who do not achieve
target blood glucose levels, suggesting a need for additional therapeutic
options.
Glucagon like peptide 1 (GLP-1) is a hormone that is predominantly released
from the small intestine in response to food intake. Activation of the GLP-1
receptor (GLP-1R) via GLP-1 stimulates insulin release, inhibits glucagon
secretion, and delays gastric emptying. In addition, GLP-1 has been shown to
increase satiety and suppress food intake.
PF 06882961 is a molecule that binds to GLP-1R that is currently being
investigated as an addition to diet and exercise to improve blood glucose
levels in adult participants with T2DM.
Study objective
The purpose of this study is to investigate how quickly and to what extent
PF-06882961 is absorbed and eliminated from the body.
The study will also investigate how safe the new compound PF-06882961 is and
how well it is tolerated when it is administered to healthy volunteers. In
addition, the taste of the oral solution of PF-06882961 will be assessed.
Study design
Subjects will be admitted to the research center 1 day before the
administration of study compound (Day -1). The actual study will consist of 2
periods. During Period 1, they will stay in the research center for a minimum
of 5 days (4 nights) and maximum of 15 days (14 nights). The second period will
start 16 days after administration of the study compound in the first period,
and subjects will stay in the research center for a maximum of 8 days (7
nights).
The volunteers will be tested for the presence of coronavirus upon admission to
the research center. Until the test results are available, they will be
separated from other participants and only have very limited contact with study
staff. This is to avoid virus spread from potentially infected participants to
other participants or to the study staff because, until the results are
available, it is not certain whether they are infected or not and can thus
potentially infect others. The test results will be available within one hour.
If they test positive for coronavirus, they cannot participate in the study.
Intervention
In Period 1 on Day 1 subjects will be given PF-06882961 with the radioactive
label as a drink of 100 mL.
In Period 2 on Day 1 subjects will be given PF-06882961 without the radioactive
label as a drink of 100 mL, similar as in Period 1. About 3 hours after the
drink, they will receive PF-06882961 with radioactive label as an intravenous
infusion of 10 mL. The infusion will last about 15 minutes.
Study burden and risks
The study compound may cause side effects. As of 27 September 2019, there have
been three completed studies with PF-06882961, including men and women of
non-childbearing potential. In 2 of these studies, PF 06882961 was taken by
healthy adult participants, and in the third study, PF-06882961 was taken by
participants with type 2 diabetes. To date, PF-06882961 has been generally safe
and well tolerated, and there have been no serious side effects reported
related to dosing of PF 06882961.
In the first study, 25 healthy participants received single doses of
PF-06882961 ranging from 3 mg to 300 mg by mouth, or a matching placebo. In
these participants, who received either PF-06882961 or placebo, 100 side
effects were reported. A majority of these side effects were deemed mild,
except for 5 side effects that were reported as *moderate* in severity. The
most common side effects were related to the gastrointestinal system and
included nausea, decreased appetite, and vomiting.
In the second study, 12 healthy participants received single doses of
PF-06882961 (of different formulations) ranging from 25 mg to 100 mg by mouth.
In these participants, 30 side effects were reported, all of which were deemed
mild. The most common side effects were headache, nausea and skin abrasion.
In the third study, participants with type 2 diabetes taking metformin were
given PF-06882961 doses ranging from 10 mg twice daily to 120 mg twice daily
(or matching placebo), or single daily doses up to 200 mg (or matching
placebo), by mouth for 28 days. In this study, 73 participants received
PF-06882961 and 25 received placebo. In
these 98 participants, 319 side effects were reported, of which a majority
(92%) were mild in severity, 7% were moderate in severity and 1% (2 of the 319)
were severe. The most frequently reported side effects were nausea, dyspepsia
(stomach upset), vomiting, diarrhea, headache, constipation and decreased
appetite. Some participants
experienced a mild increase in heart rate, ranging from 5-15 beats per minute,
with most heart rate measurements in the normal range.
In addition, in this third study, there was one participant who received
PF-06882961 120 mg twice daily who experienced 2 serious side effects during
the follow up period of the study, after completion of dosing and after
discharge from the clinical research unit. These serious side effects were
determined not to be related to PF 06882961. This participant reported symptoms
of chest pain at the follow up visit and received a cardiac evaluation, which
led to the diagnosis of an acute myocardial infarction (heart attack). The
participant admitted to symptoms of chest pain for 6 to 12 months before study
participation but did not report this when enrolling in the study. This
participant did not have symptoms of chest pain during the dosing phase of the
study. After the diagnosis of acute myocardial infarction in the follow-up
period, the participant was determined to have multi vessel coronary artery
disease (blockages in several blood vessels in the heart) and underwent
coronary artery bypass graft (CABG) surgery. After this surgery, the second
non-treatment related serious side effect of wound dehiscence (wound breakdown)
related to the surgical incision was reported.
Possible discomforts due to procedures
Drawing blood and/or insertion of the indwelling cannula may be painful or
cause some bruising.
In total, we will take about 310 milliliters of blood.
To make a heart tracing, electrodes will be pasted at specific locations on the
arms, chest and legs. Prolonged use of these electrodes can cause skin
irritation (rash and itching).
A sample for the coronavirus test will be taken from the back of the nose and
throat using a swab. Taking the sample only takes a few seconds, but can cause
discomfort and can give an unpleasant feeling. Taking a sample from the back of
the throat may cause the volunteer to gag. When the sample is taken from the
back of the nose, they may experience a stinging sensation and their eyes may
become watery.
East 42nd Street 235
New York NY 10017
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East 42nd Street 235
New York NY 10017
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Listed location countries
Age
Inclusion criteria
Age and Sex:
1. Male participants must be 18 to 54 years of age, inclusive, at the time of
signing the
informed consent document (ICD).
Type of Participant and Disease Characteristics:
2. Male participants who are overtly healthy as determined by medical
evaluation including medical history, physical examination, laboratory tests,
and ECG.
3. Participants who are willing and are able to comply with all scheduled
visits, treatment plan, laboratory tests, lifestyle considerations, and other
study procedures.
Weight:
4. Body mass index (BMI) of 17.5 to 30 kg/m2; and a total body weight >=50 kg
(110 lb).
Informed Consent:
5. Capable of giving signed informed consent as described in the protocol,
which includes compliance with the requirements and restrictions listed in the
informed consent document (ICD) and in this protocol.
Exclusion criteria
Medical Conditions:
1. Evidence or history of clinically significant hematological, renal,
endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric,
neurological, or allergic disease (including drug allergies, but excluding
untreated, asymptomatic, seasonal allergies at the time of dosing).
2. Any condition possibly affecting drug absorption (eg, gastrectomy,
cholecystectomy).
3. History of irregular bowel movements (eg, irritable bowel syndrome or
frequent episodes of diarrhea or constipation) or lactose intolerance.
4. Other acute or chronic medical or psychiatric condition including recent
(within the past year) or active suicidal ideation or behavior or laboratory
abnormality that may increase the risk associated with study participation or
investigational product administration or may interfere with the interpretation
of study results and, in the judgment of the investigator, would make the
participant inappropriate for entry into
this study.
Prior/Concomitant Therapy:
5. Use of prescription or non-prescription drugs and dietary and herbal
supplements within 14 days prior to the first dose of investigational product.
(Refer to Section 6.5 for additional details). As an exception, ibuprofen or
acetaminophen may be used at doses of <=1 g/day. Limited use of non-prescription
medications that are not believed to affect participant safety or the overall
results of the study may be permitted on a case-by-case basis following
approval by the sponsor.
Prior/Concurrent Clinical Study Experience:
6. Previous administration with an investigational drug within 60 days (or as
determined by the local requirement) preceding the first dose of
investigational product used in this study.
7. Known prior participation in a trial involving PF-06882961 or known
intolerance to a GLP-1R agonist.
Further criteria apply
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2019-002584-10-NL |
| CCMO | NL71993.056.20 |