dulaglutide 3-4 pages due by 24 hrs

A Phase 1b trial with dulaglutide (LY2189265)

INSTRUCTION: Total 3-4pages, short answer each question below

General:

1.Title of the paper and sponsor company

2.Purpose of the study

3.Brief description of the study

4.Secondary end points/additional objectives

5.Description of the drug (little drawing and text, MW) and key biological activity (in your words)

6.Inclusion criteria

7.Exclusion criteria

8.Number of cohorts, drug:placebo subject ratio, doses tested, duration of the study

9.How was the dose escalation done

Methods:

10.Blood sampling times for PK bioanalysis

11.How was the bioanalysis done, LLQ (lower limit of quantification)

12When were glucose, insulin, and C-peptide measured

13What was the composition of the test meal

14How was gastric emptying measured?

15What were the safety measurements?

Results:

16Demographics:

· How many subjects, male and female, age range

· Ethnic background and proportion in study

· Ranges of HbA1c, BMI, and fasting glucose (FG) at entry

Pharmacokinetics:

Show graph of plasma concentrations v. time

When was steady state achieved

What was the accumulation ratio

What was the Cmax to Cmin ratio?

When was the Tmax?

What was the half-life after the last dose

On week 5, at the 1 mg dose, what were the Cmax and Ctrough (rough values)

In ng/ml and nM (you may want to use the PowerPoint “guides” (View tab) to eyeball the concentrations in the graph)

Pharmacodynamics:

· Show figures with decreases in fasting (FG) and 2 h post-prandial glucose (2h-PPG)

· At what doses was the reduction in FG significant, what was the ED50?

· (The ED50 is the dose that produces half of the maximal effect in an animal or human)

· At what doses was the 2h-PPG significant?

· Pharmacodynamics (continuation):

· Show the figure with the reduction in HbA1c and body weight

· Indicate at what time are these values measured

· Was the reduction in HbA1c dose dependent?

· What was the maximal reduction in HbA1c?

· At what doses was reduction in body weight observed?

· What was the max reduction in body weight?

PK-PD relationship:

· Several of the effects occurred with the dose of 1 mg

· What Cmax and Cthrough caused the above effects (in nM)

· Is LY2189265 a potent drug?

Safety:

· Subject disposition:

· How many subjects completed the study?

· List the subjects withdrawn or with serious AE and the cause

· Adverse effects:

· List in bullets or make a little table with

· The nature of the adverse effect

· The number of AE

· In how many subject the AE appeared

· When did most of the AE appear?

· Other safety measurements:

· What effect on pulse rate did the drug have

· At what dose and when

· What was the effect of the drug on the QT interval?

· Was the drug immunogenic during the duration of the trial?

Conclusions:

· Read the conclusions on the paper

· Summarize in one-line bullets the most important aspects of the compound

· Safety

· Efficacy

· PK & convenience

· What are the authors planning to do next?

Trick question:

· After the conclusions, add a footnote showing the location (City, Country) of the investigators of this trial. This is useful to understand the ethnic composition of the study population. Also, certain locations outside the US, JP, and Western EU may have lower standards of quality and the study outcomes may be less trustworthy.