"Apply changes" will be enabled if you have "instant run" enabled and to disable instant run check https://stackoverflow.com/a/35169716/2826147
From the Android documentation: https://developer.android.com/studio/run/index.html
Apply Changes button provides a faster workflow for most incremental changes to your app. [...]
You can clickApply Changes to push certain code and resource changes to your running app without building a new APK—and, in some cases, without even restarting the current activity. [...]
Clicking Run (or Debug ) forces a cold swap and an app restart. If you make a change to the app manifest or a resource referenced by the manifest, Android Studio always pushes your changes with a full APK reinstall. [...]
Apply Changes action is available only when you meet the following conditions:
- Build your app using a debug build variant.
- Use Android plugin for Gradle version 2.3.0 or higher.
- Set minSdkVersion to 15 or higher in your app's module-level build.gradle file.
- Deploy your app to a target device running Android 5.0 (API level 21) and higher.