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Trial record 46 of 78 for:    vismodegib

A Study of Pharmacokinetic Drug Interaction Study of the Hedgehog Pathway Inhibitor GDC-0449 in Combination With Rosiglitazone or Combined Oral Contraceptive in Patients With Locally Advanced or Metastatic Solid Tumors That Are Refractory to Standard Therapy or for Whom No Standard Therapy Exists

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ClinicalTrials.gov Identifier: NCT01209143
Recruitment Status : Completed
First Posted : September 27, 2010
Results First Posted : June 29, 2015
Last Update Posted : June 29, 2015
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Solid Cancers
Interventions Drug: Vismodegib
Drug: Rosiglitazone
Drug: Norethindrone/ethinyl estradiol
Enrollment 52
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Vismodegib + Rosiglitazone Vismodegib + Oral Contraceptive
Hide Arm/Group Description

Participants received rosiglitazone 4 mg orally on Days 1 and 8 of the study. Participants also received vismodegib 150 mg orally once a day beginning on Day 2 until one of the following occurred; disease progression, intolerable toxicity, most probably attributable to vismodegib, or patient withdrawal of consent.

Vismodegib: Vismodegib was supplied in hard gelatin capsules.

Rosiglitazone: Rosiglitazone was supplied in tablets.

Participants received the oral contraceptive norethindrone 1 mg/ethinyl estradiol 35 µg (Ortho-Novum 1/35®) orally on Days 1 and 8 of the study. Participants also received vismodegib 150 mg orally once a day beginning on Day 2 until one of the following occurred; disease progression, intolerable toxicity, most probably attributable to vismodegib, or patient withdrawal of consent.

Vismodegib: Vismodegib was supplied in hard gelatin capsules.

Norethindrone/ethinyl estradiol: Norethindrone/ethinyl estradiol was supplied in tablets.

Period Title: Overall Study
Started 24 28
Completed 5 8
Not Completed 19 20
Reason Not Completed
Adverse Event             2             1
Death             0             1
Physician Decision             3             1
Lost to Follow-up             1             0
Withdrawal by Subject             2             1
Disease progression             11             16
Arm/Group Title Vismodegib + Rosiglitazone Vismodegib + Oral Contraceptive Total
Hide Arm/Group Description

Participants received rosiglitazone 4 mg orally on Days 1 and 8 of the study. Participants also received vismodegib 150 mg orally once a day beginning on Day 2 until one of the following occurred; disease progression, intolerable toxicity, most probably attributable to vismodegib, or patient withdrawal of consent.

Vismodegib: Vismodegib was supplied in hard gelatin capsules.

Rosiglitazone: Rosiglitazone was supplied in tablets.

Participants received the oral contraceptive norethindrone 1 mg/ethinyl estradiol 35 µg (Ortho-Novum 1/35®) orally on Days 1 and 8 of the study. Participants also received vismodegib 150 mg orally once a day beginning on Day 2 until one of the following occurred; disease progression, intolerable toxicity, most probably attributable to vismodegib, or patient withdrawal of consent.

Vismodegib: Vismodegib was supplied in hard gelatin capsules.

Norethindrone/ethinyl estradiol: Norethindrone/ethinyl estradiol was supplied in tablets.

Total of all reporting groups
Overall Number of Baseline Participants 24 28 52
Hide Baseline Analysis Population Description
Safety-evaluable population: All participants who received any amount of study drug (vismodegib or rosiglitazone or norethindrone/ethinyl estradiol).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 24 participants 28 participants 52 participants
62.1  (14.4) 59.2  (14.6) 60.5  (14.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 28 participants 52 participants
Female
0
   0.0%
27
  96.4%
27
  51.9%
Male
24
 100.0%
1
   3.6%
25
  48.1%
1.Primary Outcome
Title Geometric Mean Ratio of the Area Under the Plasma Concentration-time Curve From 0 to Infinity (AUC[0-inf]) of Rosiglitazone
Hide Description On Days 1 and 8, blood samples were taken prior to the administration of rosiglitazone and 30 minutes, and 1, 2, 3, 4, and 6 hours, between 8 and 12 hours, and 24 hours post-dose. Plasma concentrations of rosiglitazone were determined using a validated liquid chromatography mass spectrometry/mass spectrometry (LC MS/MS) assay. Individual and mean plasma rosiglitazone concentration versus time data were tabulated and plotted by analyte. The pharmacokinetic parameters of each analyte were calculated using standard non-compartmental methods (WinNonlin version 5.2.1, Pharsight Corp., Mountain View, CA). The geometric mean ratio of AUC(0-inf) of rosiglitazone was defined as the AUC(0-inf) of rosiglitazone on Day 8/AUC(0-inf) of rosiglitazone on Day 1.
Time Frame Pre-dose and 30 minutes, and 1, 2, 3, 4, and 6 hours, between 8 and 12 hours, and 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic population: All participants with pharmacokinetic data on Day 1 and Day 8.
Arm/Group Title Vismodegib + Rosiglitazone
Hide Arm/Group Description:

Participants received rosiglitazone 4 mg orally on Days 1 and 8 of the study. Participants also received vismodegib 150 mg orally once a day beginning on Day 2 until one of the following occurred; disease progression, intolerable toxicity, most probably attributable to vismodegib, or patient withdrawal of consent.

Vismodegib: Vismodegib was supplied in hard gelatin capsules.

Rosiglitazone: Rosiglitazone was supplied in tablets.

Overall Number of Participants Analyzed 24
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: ng/mL*hr
92.0
(87.4 to 96.8)
2.Primary Outcome
Title Geometric Mean Ratio of the Maximum Plasma Concentration (Cmax) of Rosiglitazone
Hide Description On Days 1 and 8, blood samples were taken prior to the administration of rosiglitazone and 30 minutes, and 1, 2, 3, 4, and 6 hours, between 8 and 12 hours, and 24 hours post-dose. Plasma concentrations of rosiglitazone were determined using a validated liquid chromatography mass spectrometry/mass spectrometry (LC MS/MS) assay. Individual and mean plasma rosiglitazone concentration versus time data were tabulated and plotted by analyte. The pharmacokinetic parameters of each analyte were calculated using standard non-compartmental methods (WinNonlin version 5.2.1, Pharsight Corp., Mountain View, CA). The geometric mean ratio of Cmax of rosiglitazone was defined as the Cmax of rosiglitazone on Day 8/ Cmax of rosiglitazone on Day 1.
Time Frame Pre-dose and 30 minutes, and 1, 2, 3, 4, and 6 hours, between 8 and 12 hours, and 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic population: All participants with pharmacokinetic data on Day 1 and Day 8.
Arm/Group Title Vismodegib + Rosiglitazone
Hide Arm/Group Description:

Participants received rosiglitazone 4 mg orally on Days 1 and 8 of the study. Participants also received vismodegib 150 mg orally once a day beginning on Day 2 until one of the following occurred; disease progression, intolerable toxicity, most probably attributable to vismodegib, or patient withdrawal of consent.

Vismodegib: Vismodegib was supplied in hard gelatin capsules.

Rosiglitazone: Rosiglitazone was supplied in tablets.

Overall Number of Participants Analyzed 24
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: ng/mL
93.1
(85.0 to 102)
3.Primary Outcome
Title Geometric Mean Ratio of the Area Under the Plasma Concentration-time Curve From 0 to Infinity (AUC[0-inf]) of Ethinyl Estradiol and Norethindrone
Hide Description On Days 1 and 8, blood samples were taken prior to the administration of the contraceptive norethindrone 1 mg/ethinyl estradiol 35 µg (Ortho-Novum 1/35®) and 30 minutes, and 1, 2, 3, 4, and 6 hours, between 8 and 12 hours, and 24 hours post-dose. Plasma concentrations of ethinyl estradiol and norethindrone were determined using a validated liquid chromatography mass spectrometry/mass spectrometry (LC MS/MS) assay. Individual and mean plasma ethinyl estradiol and norethindrone concentration versus time data were tabulated and plotted by analyte. The pharmacokinetic parameters of each analyte were calculated using standard non-compartmental methods (WinNonlin version 5.2.1, Pharsight Corp., Mountain View, CA). The geometric mean ratios of AUC(0-inf) of ethinyl estradiol and norethindrone were defined as the ratios of AUC(0-inf) of ethinyl estradiol and norethindrone on Day 8 divided by AUC(0-inf) of ethinyl estradiol and norethindrone on Day 1, respectively.
Time Frame Pre-dose and 30 minutes, and 1, 2, 3, 4, and 6 hours, between 8 and 12 hours, and 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic population: All participants with pharmacokinetic data on Day 1 and Day 8.
Arm/Group Title Vismodegib + Oral Contraceptive
Hide Arm/Group Description:

Participants received the oral contraceptive norethindrone 1 mg/ethinyl estradiol 35 µg (Ortho-Novum 1/35®) orally on Days 1 and 8 of the study. Participants also received vismodegib 150 mg orally once a day beginning on Day 2 until one of the following occurred; disease progression, intolerable toxicity, most probably attributable to vismodegib, or patient withdrawal of consent.

Vismodegib: Vismodegib was supplied in hard gelatin capsules.

Norethindrone/ethinyl estradiol: Norethindrone/ethinyl estradiol was supplied in tablets.

Overall Number of Participants Analyzed 27
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: ng/mL*hr
Ethinyl estradiol
99.6
(92.9 to 107)
Norethindrone
123
(115 to 131)
4.Primary Outcome
Title Geometric Mean Ratio of the Maximum Plasma Concentration (Cmax) of Ethinyl Estradiol and Norethindrone
Hide Description On Days 1 and 8, blood samples were taken prior to the administration of the contraceptive norethindrone 1 mg/ethinyl estradiol 35 µg (Ortho-Novum 1/35®) and 30 minutes, and 1, 2, 3, 4, and 6 hours, between 8 and 12 hours, and 24 hours post-dose. Plasma concentrations of ethinyl estradiol and norethindrone were determined using a validated liquid chromatography mass spectrometry/mass spectrometry (LC MS/MS) assay. Individual and mean plasma ethinyl estradiol and norethindrone concentration versus time data were tabulated and plotted by analyte. The pharmacokinetic parameters of each analyte were calculated using standard non-compartmental methods (WinNonlin version 5.2.1, Pharsight Corp., Mountain View, CA). The geometric mean ratios of Cmax of ethinyl estradiol and norethindrone were defined as the ratios of Cmax of ethinyl estradiol and norethindrone on Day 8 divided by Cmax of ethinyl estradiol and norethindrone on Day 1, respectively.
Time Frame Pre-dose and 30 minutes, and 1, 2, 3, 4, and 6 hours, between 8 and 12 hours, and 24 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic population: All participants with pharmacokinetic data on Day 1 and Day 8.
Arm/Group Title Vismodegib + Oral Contraceptive
Hide Arm/Group Description:

Participants received the oral contraceptive norethindrone 1 mg/ethinyl estradiol 35 µg (Ortho-Novum 1/35®) orally on Days 1 and 8 of the study. Participants also received vismodegib 150 mg orally once a day beginning on Day 2 until one of the following occurred; disease progression, intolerable toxicity, most probably attributable to vismodegib, or patient withdrawal of consent.

Vismodegib: Vismodegib was supplied in hard gelatin capsules.

Norethindrone/ethinyl estradiol: Norethindrone/ethinyl estradiol was supplied in tablets.

Overall Number of Participants Analyzed 27
Measure Type: Number
Number (90% Confidence Interval)
Unit of Measure: ng/mL
Ethinyl estradiol
105
(94.4 to 116)
Norethindrone
112
(101 to 124)
Time Frame [Not Specified]
Adverse Event Reporting Description Safety-evaluable population: All participants who received any amount of study drug (vismodegib or rosiglitazone or norethindrone/ethinyl estradiol).
 
Arm/Group Title Vismodegib + Rosiglitazone Vismodegib + Oral Contraceptive
Hide Arm/Group Description

Participants received rosiglitazone 4 mg orally on Days 1 and 8 of the study. Participants also received vismodegib 150 mg orally once a day beginning on Day 2 until one of the following occurred; disease progression, intolerable toxicity, most probably attributable to vismodegib, or patient withdrawal of consent.

Vismodegib: Vismodegib was supplied in hard gelatin capsules.

Rosiglitazone: Rosiglitazone was supplied in tablets.

Participants received the oral contraceptive norethindrone 1 mg/ethinyl estradiol 35 µg (Ortho-Novum 1/35®) orally on Days 1 and 8 of the study. Participants also received vismodegib 150 mg orally once a day beginning on Day 2 until one of the following occurred; disease progression, intolerable toxicity, most probably attributable to vismodegib, or patient withdrawal of consent.

Vismodegib: Vismodegib was supplied in hard gelatin capsules.

Norethindrone/ethinyl estradiol: Norethindrone/ethinyl estradiol was supplied in tablets.

All-Cause Mortality
Vismodegib + Rosiglitazone Vismodegib + Oral Contraceptive
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Vismodegib + Rosiglitazone Vismodegib + Oral Contraceptive
Affected / at Risk (%) Affected / at Risk (%)
Total   0/24 (0.00%)   0/28 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Vismodegib + Rosiglitazone Vismodegib + Oral Contraceptive
Affected / at Risk (%) Affected / at Risk (%)
Total   22/24 (91.67%)   20/28 (71.43%) 
Blood and lymphatic system disorders     
Anaemia  1  1/24 (4.17%)  2/28 (7.14%) 
Gastrointestinal disorders     
Constipation  1  7/24 (29.17%)  7/28 (25.00%) 
Nausea  1  4/24 (16.67%)  8/28 (28.57%) 
Vomiting  1  1/24 (4.17%)  4/28 (14.29%) 
Abdominal pain  1  2/24 (8.33%)  2/28 (7.14%) 
Diarrhoea  1  2/24 (8.33%)  1/28 (3.57%) 
Abdominal tenderness  1  0/24 (0.00%)  2/28 (7.14%) 
Dry mouth  1  2/24 (8.33%)  0/28 (0.00%) 
General disorders     
Fatigue  1  7/24 (29.17%)  5/28 (17.86%) 
Investigations     
Weight decreased  1  3/24 (12.50%)  1/28 (3.57%) 
Metabolism and nutrition disorders     
Decreased appetite  1  4/24 (16.67%)  4/28 (14.29%) 
Musculoskeletal and connective tissue disorders     
Muscle spasms  1  13/24 (54.17%)  10/28 (35.71%) 
Back pain  1  2/24 (8.33%)  1/28 (3.57%) 
Pain in extremity  1  2/24 (8.33%)  1/28 (3.57%) 
Nervous system disorders     
Dysgeusia  1  9/24 (37.50%)  9/28 (32.14%) 
Headache  1  3/24 (12.50%)  1/28 (3.57%) 
Hypogeusia  1  2/24 (8.33%)  0/28 (0.00%) 
Psychiatric disorders     
Insomnia  1  3/24 (12.50%)  1/28 (3.57%) 
Anxiety  1  1/24 (4.17%)  2/28 (7.14%) 
Respiratory, thoracic and mediastinal disorders     
Pleural effusion  1  0/24 (0.00%)  3/28 (10.71%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  3/24 (12.50%)  2/28 (7.14%) 
Night sweats  1  1/24 (4.17%)  3/28 (10.71%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (14.1)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
Results Point of Contact
Name/Title: Medical Communications
Organization: Genentech, Inc.
Phone: 800 821-8590
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01209143     History of Changes
Other Study ID Numbers: SHH4593g
GO01353 ( Other Identifier: Hoffmann-La Roche )
First Submitted: September 23, 2010
First Posted: September 27, 2010
Results First Submitted: June 5, 2015
Results First Posted: June 29, 2015
Last Update Posted: June 29, 2015