0001104659-08-034627.txt : 20080520 0001104659-08-034627.hdr.sgml : 20080520 20080520160604 ACCESSION NUMBER: 0001104659-08-034627 CONFORMED SUBMISSION TYPE: 8-K PUBLIC DOCUMENT COUNT: 3 CONFORMED PERIOD OF REPORT: 20080520 ITEM INFORMATION: Regulation FD Disclosure ITEM INFORMATION: Financial Statements and Exhibits FILED AS OF DATE: 20080520 DATE AS OF CHANGE: 20080520 FILER: COMPANY DATA: COMPANY CONFORMED NAME: THERAVANCE INC CENTRAL INDEX KEY: 0001080014 STANDARD INDUSTRIAL CLASSIFICATION: PHARMACEUTICAL PREPARATIONS [2834] IRS NUMBER: 943265960 STATE OF INCORPORATION: DE FISCAL YEAR END: 1231 FILING VALUES: FORM TYPE: 8-K SEC ACT: 1934 Act SEC FILE NUMBER: 000-30319 FILM NUMBER: 08848800 BUSINESS ADDRESS: STREET 1: 901 GATEWAY BLVD CITY: SOUTH SAN FRANCISCO STATE: CA ZIP: 94080 BUSINESS PHONE: 6508086000 MAIL ADDRESS: STREET 1: 901 GATEWAY BLVD CITY: S. SAN FRANCISCO STATE: CA ZIP: 94080 FORMER COMPANY: FORMER CONFORMED NAME: ADVANCED MEDICINE INC DATE OF NAME CHANGE: 20000302 8-K 1 a08-14726_18k.htm 8-K

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, DC 20549

FORM 8-K

Current Report Pursuant

to Section 13 or 15(d) of the

Securities Exchange Act of 1934

Date of Report (Date of earliest event Reported): May 20, 2008

THERAVANCE, INC.

(Exact Name of Registrant as Specified in its Charter)

Delaware

(State or Other Jurisdiction of
Incorporation)

000-30319

(Commission File Number)

94-3265960

(I.R.S. Employer Identification Number)

901 Gateway Boulevard
South San Francisco, California 94080
(650) 808-6000

(Addresses, including zip code, and telephone numbers, including area code, of principal executive offices)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):

o Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

o Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

o Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

o Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Item 7.01 Regulation FD Disclosure.

The information in this Current Report (including Exhibits 99.1and 99.2) is being furnished and shall not be deemed “filed” for the purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liabilities of that Section. The information in this Current Report (including Exhibits 99.1 and 99.2) shall not be incorporated by reference into any registration statement or other document pursuant to the Securities Act of 1933, as amended, except as shall be expressly set forth by specific reference in such filing.

Today at Digestive Disease Week in San Diego, California, posters presenting information from Theravance’s Phase 2 dose-ranging clinical trial of TD-5108 in patients with chronic idiopathic constipation will be available for viewing. The abstracts contained in the two posters are attached hereto as Exhibits 99.1 and 99.2 and are incorporated herein by reference.

Item 9.01 Financial Statements and Exhibits.

(d)	Exhibits

	Exhibit	Description

	Exhibit 99.1	Abstract regarding response rates in Phase 2 clinical study of TD-5108

	Exhibit 99.2	Abstract regarding secondary endpoints in Phase 2 clinical study of TD-5108

SIGNATURE

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.


	THERAVANCE, INC.

Date: May 20, 2008	By:	/s/ Rick E Winningham

		Rick E Winningham
		Chief Executive Officer

EXHIBIT INDEX

Exhibit No.		Exhibit
99.1		Abstract regarding response rates in Phase 2 clinical study of TD-5108
99.2		Abstract regarding secondary endpoints in Phase 2 clinical study of TD-5108

EX-99.1 2 a08-14726_1ex99d1.htm EX-99.1

Exhibit 99.1

TD-5108, a Selective 5-HT4 Agonist, Is Consistently Better Than Placebo Regardless of Response Definition in Patients with Chronic Constipation

Michael R Goldberg(1), Yu-Ping Li(1), Kenneth Pitzer(1), John F Johanson(2), Allen W Mangel(3), Michael M Kitt(1)
1. Clinical Pharmacology, Theravance, Inc., South San Francisco, CA, USA, 2. University of Illinois College of Medicine, Rockford, IL, USA, 3. RTI-Health Solutions, Research Triangle, NC, USA

TD-5108 is a highly selective, full agonist at the human 5-HT4 receptor. Multiple response definitions were pre-specified in a Phase 2 dose-ranging clinical trial of TD-5108 in patients (pts) with chronic idiopathic constipation (CIC). TD-5108 was consistently better than placebo in response rates across response definitions.

Results: Treatment groups were balanced for baseline characteristics. The average (avg) numbers of SBM and complete SBM (CSBM) at baseline were 1.2 and 0.25/wk, respectively. Analyses of the response definitions are summarized below (n=number of patients treated for at least 7 days). Response rates using each definition were significantly greater than placebo for all TD-5108 doses. The lowest PBO response rates (< 10%) were seen with definitions that incorporated CSBM frequency > 3/wk; these response definitions were also associated with the greatest differences between TD-5108 and PBO—5-fold or greater.

Conclusion: In this study in pts with CIC treated for 4 wks, the percent response to TD-5108 was greater than that to placebo regardless of response definition. The most robust differentiation of responses to TD-5108 vs PBO was achieved with< font size="1" style="font-size:8.0pt;"> response definitions incorporating > 3CSBM/wk.

	PBO (n=98)	15 mg (n=95)	30 mg (n=91)	50 mg (n=84)	Max Fold Difference from PBO

% with > 1 SBM/wk increase in Wk 4	45%	82% p<0.001	63% p=0.028	76% p<0.001	1.82

% with an avg of >3 SBM/wk and an avg increase of > 1 SBM/wk	43%	75% p<0.001	66% p<0.002	64% p<0.004	1.74

% with >3 SBM/wk in Wk 4	41%	78% p<0.001	60% p=0.015	72% p<0.001	1.90

% with > 1 CSBM/wk increase in Wk 4	29%	59% p<0.001	45% p=0.033	54% p=0.002	2.03

% with > 1 SBM/wk increase for all 4 wks	25%	69% p<0.001	49% p=0.002	71% p<0.001	2.84

% with >3 SBM/wk for all 4 wks	22%	60% p<0.001	42% p=0.007	61% p<0.001	2.77

% with > 1 CSBM/wk increase for all 4 wks	13%	42% p<0.001	30% p=0.010	39% p<0.001	3.23

% with >3 CSBM/wk in Wk 4	9%	48% p<0.001	27% p=0.004	37% p<0.001	5.33

% with an avg of >3 CSBM/wk and an avg increase of > 1 CSBM/wk	7%	44% p<<0.001	30% p<0.001	35% p<0.001	6.29

% with >3 CSBM/wk for all 4 wks	5%	27% p<0.001	19% p=0.006	21% p=0.002	5.40

EX-99.2 3 a08-14726_1ex99d2.htm EX-99.2

Exhibit 99.2

In Patients with Chronic Constipation, TD-5108, a Selective 5-HT4 Agonist with High Intrinsic Activity, Relieves Straining and Bloating, Normalizes Stool Consistency and Reduces Laxative Use

Michael R Goldberg(1), Yu-Ping Li(1), Allen W Mangel(3), John F Johanson(2), Kenneth Pitzer(1), Michael M Kitt(1)
1. Clinical Pharmacology, Theravance, Inc., South San Francisco, CA, USA, 2. University of Illinois College of Medicine, Rockford, IL, USA, 3. RTI Health Solutions, Research Triangle, NC, USA

TD-5108 is a potent, highly selective, full agonist at the human 5-HT4 receptor. A Phase 2 dose-ranging clinical trial was conducted to investigate the efficacy and safety of TD-5108 in patients (pts) with chronic idiopathic constipation (CIC). Increases in bowel movement frequency in comparison to placebo (PBO) associated with TD-5108 administration have previously been reported#. We report here effects of TD-5108 on other manifestations of CIC, including stool consistency, straining, bloating and use of rescue laxative.

Methods: This double-blind, randomized, PBO-controlled, parallel-group, multicenter trial enrolled 401 adult pts (age 18-64 years) at 48 U.S. sites. Eligible pts (<3 spontaneous bowel movements [SBM]/week [wk] during a 2-wk baseline period) were randomized to receive TD-5108 15, 30, or 50 mg, or PBO once daily for 4 wks. Rescue laxative (bisacodyl) could be used every 96 hours if necessary. Bowel function and clinical symptoms were recorded daily via IVRS. Use of rescue laxative, stool consistency, bloating (yes or no) and straining (3-point scale (0=none, 1=acceptable, 2=too much)) were assessed in addition to stool frequency. In the analyses below, n=number of patients in each group treated for at least 7 days.

Results: Treatment groups were balanced for baseline characteristics including stool frequency. During the 2 week baseline period, ~20% had normal stool consistency (Bristol score 3-5), ~80% reported straining, 85-95%% reported bloating and laxatives were used by about 65% of patients. Stool consistency, CIC symptoms and laxative use during treatment compared to PBO are summarized below. The results show that, at all doses tested, there were significant increases in the proportion of patients with normal stool consistency, decreases in straining and bloating, and reduced rescue laxative use.

Conclusion: In this study of pts with CIC treated for 4 wks, treatment with TD-5108 was associated with statistically and clinically significant relief of straining and bloating, normalized stool consistency, and reduced use of rescue laxative. #Am. College Gastroenterology, Oct, 2007

	PBO (n=98)	15 mg (n=95)	30 mg (n= 91)	50 mg (n= 84)

% with average Bristol score of 3-5 in Wk 4	27%	51% P=0.0022	45% P=0.0188	57% P=0.0003

% with average straining score of <1 (no straining) in Wk 4	33%	65% P<0.0001	54% P=0.0045	68% P=0.0002

% with bloating in Wk 4	92%	73% P=0.0014	80% P=0.0288	63% P<0.0001

% with no laxative use over 4–week treatment period	36%	53% P<0.0179	57% P=0.0031	51% P=0.0354

Median hrs to first rescue laxative during 4-wk treatment period (95% CI)	292 (200, 394)	NA## (373, NA) P=0.026	NA (469, NA) P<0.0044	631 (269, NA) P<0.0880

^##NA—could not be calculated