| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10029883 |
| E.1.2 | Term | Obesity |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective of the study is to find the appropriate, clinically relevant dosages (among the 5, 10, and 15 mg twice-daily dosages) of JNJ-16269110 by assessing mean changes in body weight from baseline to Week 12, compared to placebo. |
|
| E.2.2 | Secondary objectives of the trial |
To estimate the dose-response relationship between the different dosages of JNJ-16269110 and the decrease in body weight from baseline to Week 12
To estimate the effect on weight loss of different JNJ-16269110 dosages versus placebo as expressed by mean percent change from baseline in body weight and in body mass index (BMI), and the percentage of subjects who lose at least 5% or 10% of their initial body weight
To estimate changes in body composition using anthropometric measurements and by means of Dual X Ray Absorptiometry (DEXA [only at selected sites] to explore if weight loss is predominantly due to loss of fat mass
To explore changes in obesity-associated comorbidities as assessed by glucose homeostasis, fasting lipid profile, and systolic and diastolic blood pressure
To explore the effect of JNJ-16269110 on changes in levels of PYY, GLP 1, and oxyntomodulin
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
FINAL: 07 August 2007 47
• Men or women
• Between 18 and 65 years of age, inclusive
• Women must be:
• postmenopausal, defined as having a last menstrual period at least
1 year before screening with a serum follicle-stimulating hormone
(FSH) level consistent with postmenopausal status
• or surgically incapable of childbearing (have had a hysterectomy or
bilateral oophorectomy or tubal ligation or otherwise incapable of
pregnancy)
• or if sexually active, be practicing an effective method of birth control
(e.g. spermicide plus barrier, hormonal contraceptive, intrauterine
device, or a partner with a vasectomy);
• or sexually abstinent
• Women of childbearing potential must be practicing an acceptable
method of birth control (as previously defined) and have had a negative
urine pregnancy test at screening as well as at the baseline visit before
receiving study drug, which will be followed immediately by a serum
beta-human chorionic gonadotropin (β-hCG) test. Subjects may be
admitted to the study if the urine pregnancy test is negative, but will be
discontinued immediately should the serum results be positive. Only a
serum test is necessary at the end of the double-blind treatment phase.
During the double-blind phase, a pregnancy test will be performed if
pregnancy is suspected. Additional pregnancy tests may be performed at
the discretion of the investigator.
• Must be obese or overweight at screening (start of run-in period), defined
as:
• BMI ≥30 kg/m2 and <50 kg/m2 or
• BMI ≥27 kg/m2 and <50 kg/m2 in the presence of controlled
hypertension and/or treated or untreated dyslipidemia. For subjects
receiving antihypertensive and/or hypolipidemic medications, these
should have been at a stable dosage for at least 2 months before the
start of the run-in period. There should be no anticipated changes to
JNJ-16269110: Clinical Protocol R256918OBE2001
antihypertensive or lipid-lowering medications during the course of the
study.
• Controlled hypertension is defined as a diastolic blood pressure
<100 mmHg and a systolic blood pressure <160 mmHg, in the
presence of antihypertensive drug treatment.22
• For subjects who are not on lipid-lowering drugs, dyslipidemia is
defined as LDL-C ≥3.4 mmol/L (130 mg/dL), HDL-C <1 mmol/L (40
mg/dL) for men or <1.3 mmol/L (50 mg/dL) for women, or
triglycerides ≥1.7 mmol/L (150 mg/dL).23
• If subjects are clinically diagnosed with dyslipidemia as a result of
screening assessments, they can only continue in the run-in phase of
the study if in the clinical judgment of the investigator initiation of
lipid-lowering therapy is not required either immediately or during the
course of the study.
• A stable weight, i.e., increasing or decreasing not more than 5 kg in the
3 months before the start of the run-in period.
• Consumption of breakfast and dinner on a daily basis
• Ability to swallow the intact capsule (17.5 mm in length and 9.1 mm in
diameter) with water, as judged by e.g. the subject's history of having no
difficulty with swallowing e.g. capsules or intact tablets.
• Fasting plasma glucose24 <7.0 mmol/L (126 mg/dL) at screening; in cases
in which there is doubt concerning fasting conditions, a 1-time repeat of
the fasting plasma glucose is allowed (fasting is defined as no caloric
intake for at least 8 hours before the test)
• Willing to adhere to the prohibitions and restrictions specified in this
protocol
• Subjects must have signed an informed consent document indicating that
they understand the purpose of and procedures required for the study and
are willing to participate in the study.
• To participate in the optional pharmacogenomic component of this study,
subjects (or their legally acceptable representative) must have signed the
informed consent for pharmacogenomic research indicating willingness to
participate in the pharmacogenomic component of the study (where local
regulations permit). Subjects must also consent separately for blood
samples for the future analysis of ALT isoforms. Refusal to consent for
either component does not exclude a subject from participation in the
clinical study. |
|
| E.4 | Principal exclusion criteria |
FINAL: 07 August 2007 49
• History of obesity with a known cause (e.g., Cushing’s disease)
• History of anorexia nervosa, bulimia, or binge-eating disorder
• An established diagnosis of diabetes mellitus or treatment with glucoselowering
prescription drugs at screening
• Prior exposure or known contraindication or hypersensitivity to
JNJ-16269110
• History of weight-reducing diet or receiving any drugs to treat obesity
within the 3 months prior to screening
• Treatment with any investigational drug or device within 1 month before
the start of the run-in period
• History or evidence of liver disease, including cirrhosis or nonalcoholic
steatohepatitis/non-alcoholic fatty liver disease,
• History of HIV or presence of hepatitis C antibodies or positive
hepatitis B serology (refer to Attachment 2, Interpretation of Hepatitis B
Results for Enrolling Subjects at screening)
• History of clinically significant gastro-intestinal disease (including but
not limited to gluten- and non-gluten-induced enteropathy, inflammatory
bowel disease, malabsorption syndromes)
• History of major gastro-intestinal surgery other than appendectomy or
uncomplicated cholecystectomy.
• Previous gastric restrictive surgery or other surgical procedures to induce
weight loss
• Liposuction within the last 3 months before screening
• Pregnant or nursing women, or women who plan to become pregnant
during the study
• History of significant cardiovascular disease, including a history of
myocardial infarction (MI), unstable angina and cerebrovascular accident
(CVA) within 6 months of enrollment.
• History of clinically significant cardiac valvular disease, or congestive
heart failure (cardiovascular disability functional Class III-IV according
to the New York Heart Association Classification of Cardiac Disease25;
refer to Attachment 3)
• 12-lead ECG showing evidence of clinically significant heart rhythm or
conduction abnormality at screening or baseline.
• An average of 3 seated readings where diastolic blood pressure
≥100 mmHg or a systolic blood pressure ≥160 mmHg at screening
• Thyroid-stimulating hormone (TSH) >1.5 times ULN at screening.
Subjects on medication for hypothyroidism should have been on a stable
JNJ-16269110: Clinical Protocol R256918OBE2001
FINAL: 07 August 2007 50
dosage for at least 3 months before enrollment (the start of the run-in
period).
• A significant change in smoking habits within 3 months of the start of the
run-in period; subjects planning to alter smoking habits during the course
of the study
• Malignancy or a history of a malignancy within 5 years before the start of
the run-in period, other than basal cell carcinomas of the skin or in situ
cervical carcinoma
• History or evidence of clinically significant abnormal values for
hematology, coagulation, or clinical biochemistry.
• Increased liver function tests,
• ALT above 1.5 X ULN
• ALT above ULN but less than 1.5 X ULN with a concomitant increase
of AST, bilirubin, alkaline phosphatase or LDH above 1.5 X ULN or
GGT above 2x ULN at screening.
• Increased creatinine kinase (CK) above ULN in subjects who take lipid
lowering agents and CK level above 2 x ULN in subjects who do not take
lipid lowering agents at screening visit.
• Fasting TG >33.3 mmol/L (600 mg/dL) at screening. A 1-time repeat of
the fasting triglycerides is allowed (fasting is defined as no caloric intake
for at least 8 hours before the test)
• Evidence of renal impairment (serum creatinine >133 µmol/L (1.5
mg/dL) in men, >124 µmol/L (1.4 mg/dL) in women)
• History of drug or alcohol abuse within the previous 2 years
• Alcohol consumption exceeding 4 units per day for men or 3 units per day
for women; 1 unit is defined as 330 mL beer, 100 mL wine, or 30 mL
distilled spirits or the equivalent of this26
• Receiving any excluded medication (refer to Section 8, Concomitant
Therapy)
• Any condition that in the opinion of the investigator would complicate or
compromise the study, or the wellbeing of the subject
• Women of childbearing potential must continue to practice an acceptable
method of birth control.
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| To evaluate the efficacy, safety and tolerability of JNJ-16269110 |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 18 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
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