Thorough QT Study # 1
IDENTIFICATION : E-HOL-03-0102-005

Study Design: The study was a double-blind, randomised, 5-way crossover study. The study consisted of a single cohort of 35 subjects. Each subject was randomised to one of 10 possible sequences of treatment and received a single dose of Unknown Compound (UnC): 30mg / 100mg and 300mg. Placebo or moxifloxacin was given on five occasions, each being 10-14 days apart. During each study period subjects were resident for two nights/three days and a follow-up visit occurred 10-14 days after the final administration. A run-in day, independent from the randomisation was included in Period 3 requiring an additional one night/one day residency during which subjects were administered a single blinded placebo dose.

Inclusion Criteria: Healthy male and female subjects, between age 18 to 55 years, inclusive body mass index is approximatively 18 to 30 Kg/m*m and total body weight >50kg were enrolled in the study.

Study Treatment: A single oral dose of UnC tablets (30, 100 and 300mg), placebo or a single moxifloxacin tablet (400mg) was administered on five separate occasions with 10-14 days between each study period.

Pharmacokinetic and Pharmacodynamic Evaluations: Pharmacokinetic evaluations: Blood samples were obtained from subjects at protocol specified intervals of time to calculate the AUC24, Cmax, and Tmax for UnC. Pharmacodynamic evaluations: ECG measurements were recorded at the protocol specified times before the pharmacokinetic blood samples were collected (within five minutes of the ECG), after subjects had been resting semi-recumbent for at least 10 minutes. Holter monitoring was performed on Day 1 (Period 3 only) and Day 1 (all periods) from pre-dose to approximately eight hours post-dose.

The QRS detection and beat annotations were obtained using Philips Holter System.

File Naming Convention: Each filename is composed by Individual ID and arm ID. For instance, the Holter ECG from the individual ID=33, recorded in the placebo arm is called "33-pbo". Three arms from this study are included in the warehouse : 300mg,moxi and pbo corresponding to the arms fro the unknown compound, moxifloxacin and placebo, respectively.

Global Epochs: Each Holter recordings includes an epoch called "4-hour post dosing" which indicates the start time of dosing and the end time of a 4-hour long time interval after dosing.

Number of Leads: 3 (EASI lead configuration)

Sampling Frequency : 200Hz

Amplitude Resolution: 4.9 microV

Clinical Information: The list of clinical information available for this study are described int he following table:

5	Unique subject number within trial (SUBJID)
6	Collection date (COLLDATE)
7	Age (AGE)
8	Units for Age (AGEUNITS)
9	Age in Days (AGEDAY)
10	Age in weeks (AGEWEEK)
11	Age in months (AGEMTH)
12	Age in Years (AGEYR)
14	Height in cm (HT)
15	Height raw (HTRAW)
16	Height raw units (HTUNI)
17	Weight in kg (WT)
18	Weight raw (WTRAW)
19	Weight raw units (WTUNI)
20	Race (RACES)
21	Text for other race (RACEOTH)
22	Original textual value of race (XRACES)
23	Gender code (SEX)
24	Original textual value of SEX (XSEX)
27	Raw value of beer consumed (ALCBEERR)
28	Units for raw beer consumed (ALCBEERU)
30	Raw value of wine consumed (ALCWINER)
31	Units for raw wine consumed (ALCWINEU)
33	Spirits/liquor consumed-raw (ALCOTHR)
34	Spirits/liquor consumed-units (ALCOTHU)
36	Does the patient drink (ALCHIST2)
37	Subject started smoking-years (STDUR)
38	Subject started smoking-raw (STDURRAW)
39	Subject started smoking-units (STDURUNI)
40	Time since stopped smoking-years (SPDUR)
41	Time since stopped smoking-raw (SPDURRAW)
42	Time since stopped smoking-units (SPDURUNI)
43	Nicotine Usage (SMOKE)
44	Smoking classification (SMKCLASS)
45	Amount Cigarettes smoked per day (SMKCIGTA)
46	Raw amount of cigarettes smoked (SMKCIGTR)
47	Cigarettes smoked-units (SMKCIGTU)
48	amount Cigars smoked per day (SMKCIGA)
49	Cigars smoked per day (SMKCIGR)
50	Cigars smoked-units (SMKCIGU)
51	Amount of Pipes smoked per day (SMKPIPEA)
52	Raw amount of pipes smoked (SMKPIPER)
53	Pipes smoked-units (SMKPIPEU)
54	Smokes Cigarellos (SMKCRL)
55	Cigarellos per day (SMKCRLA)
56	Chew Tobacco (SMKCTB)
57	Chew tobacco consumed per day (SMKCTBA)
58	Did the subject quit due to poor health (SMKQPH)
59	Visit designator (VISIT_ID)
60	Country (CNTRYCOD)
61	Info sheet handed to patient? (INFSHEET)
62	Info sheet handed to patient? (INFSHEE2)
63	Reason info sheet not handed on (INFSHTT)
89	Visit (VISIT)
90	COLLDAT2 (COLLDAT2)
91	VISIT2 (VISIT2)
99	Repeat # (REPEATSN)
107	SUBJECT SMOKE CIGARS-DVN (SMKCIG)
108	SUBJECT SMOKE CIGARETTES-DVN (SMKCIGT)
109	SUBJECT SMOKE A PIPE-DVN (SMKPIPE)